Author: "McCarroll SA" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"McCarroll SA"' showing total 235 results

Start Over Author "McCarroll SA"

235 results on '"McCarroll SA"'

1. Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.

Author: Charney, AW, Ruderfer, DM, Stahl, EA, Moran, JL, Chambert, K, Belliveau, RA, Forty, L, Gordon-Smith, K, Di Florio, A, Lee, PH, Bromet, EJ, Buckley, PF, Escamilla, MA, Fanous, AH, Fochtmann, LJ, Lehrer, DS, Malaspina, D, Marder, SR, Morley, CP, Nicolini, H, Perkins, DO, Rakofsky, JJ, Rapaport, MH, Medeiros, H, Sobell, JL, Green, EK, Backlund, L, Bergen, SE, Juréus, A, Schalling, M, Lichtenstein, P, Roussos, P, Knowles, JA, Jones, I, Jones, LA, Hultman, CM, Perlis, RH, Purcell, SM, McCarroll, SA, Pato, CN, Pato, MT, Craddock, N, Landén, M, Smoller, JW, and Sklar, P
Subjects: Chromosomes, Human, Pair 10, Humans, Aminopeptidases, Ankyrins, Calmodulin-Binding Proteins, Calcium Channels, L-Type, Cytoskeletal Proteins, Nerve Tissue Proteins, Nuclear Proteins, Case-Control Studies, Bipolar Disorder, Psychotic Disorders, Genotype, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Chromosomes, Human, Pair 10, Calcium Channels, L-Type, Polymorphism, Single Nucleotide, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.
Published: 2017

2. Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.

Author: Rees, E, Kirov, G, Walters, JT, Richards, AL, Howrigan, D, Kavanagh, DH, Pocklington, AJ, Fromer, M, Ruderfer, DM, Georgieva, L, Carrera, N, Gormley, P, Palta, P, Williams, H, Dwyer, S, Johnson, JS, Roussos, P, Barker, DD, Banks, E, Milanova, V, Rose, SA, Chambert, K, Mahajan, M, Scolnick, EM, Moran, JL, Tsuang, MT, Glatt, SJ, Chen, WJ, Hwu, H-G, Taiwanese Trios Exome Sequencing Consortium, Neale, BM, Palotie, A, Sklar, P, Purcell, SM, McCarroll, SA, Holmans, P, Owen, MJ, and O'Donovan, MC
Subjects: Taiwanese Trios Exome Sequencing Consortium, Humans, Genetic Predisposition to Disease, Case-Control Studies, Family, Schizophrenia, Gene Frequency, Genotype, Heterozygote, Homozygote, Genes, Recessive, Female, Male, Exome, Voltage-Gated Sodium Channels, Genes, Recessive, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband-parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽ 1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P = 1.5 × 10(-)(4)). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽ 0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P = 0.018) and de novo mutations (P = 0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N = 614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.
Published: 2015

3. Statistical and functional convergence of common and rare genetic influences on autism at chromosome 16p

Author: Weiner, Daniel J., Ling, Emi, Erdin, Serkan, Tai, Derek J.C., Yadav, Rachita, Grove, Jakob, Fu, Jack M., Nadig, Ajay, Carey, Caitlin E., Baya, Nikolas, Bybjerg-Grauholm, Jonas, McCarroll, SA, Robinson, EB, Weiner, Daniel J., Ling, Emi, Erdin, Serkan, Tai, Derek J.C., Yadav, Rachita, Grove, Jakob, Fu, Jack M., Nadig, Ajay, Carey, Caitlin E., Baya, Nikolas, Bybjerg-Grauholm, Jonas, McCarroll, SA, and Robinson, EB
Abstract: The canonical paradigm for converting genetic association to mechanism involves iteratively mapping individual associations to the proximal genes through which they act. In contrast, in the present study we demonstrate the feasibility of extracting biological insights from a very large region of the genome and leverage this strategy to study the genetic influences on autism. Using a new statistical approach, we identified the 33-Mb p-arm of chromosome 16 (16p) as harboring the greatest excess of autism’s common polygenic influences. The region also includes the mechanistically cryptic and autism-associated 16p11.2 copy number variant. Analysis of RNA-sequencing data revealed that both the common polygenic influences within 16p and the 16p11.2 deletion were associated with decreased average gene expression across 16p. The transcriptional effects of the rare deletion and diffuse common variation were correlated at the level of individual genes and analysis of Hi-C data revealed patterns of chromatin contact that may explain this transcriptional convergence. These results reflect a new approach for extracting biological insight from genetic association data and suggest convergence of common and rare genetic influences on autism at 16p.
Published: 2022

4. Skewed X-inactivation is common in the general female population

Author: Shvetsova, E, Sofronova, A, Monajemi, R, Gagalova, K, Draisma, HHM, White, SJ, Santen, GWE, Lopes, SMCDS, Heijmans, BT, Van Meurs, J, Jansen, R, Franke, L, Kielbasa, SM, Den Dunnen, JT, 't Hoen, PAC, Boomsma, DI, Pool, R, Van Dongen, J, Hottenga, JJ, Van Greevenbroek, MMJ, Da Stehouwer, C, Van der Kallen, CJH, Schalkwijk, CG, Wijmenga, C, Zhernakova, S, Tigchelaar, EF, Slagboom, PE, Beekman, M, Deelen, J, Van Heemst, D, Veldink, JH, Van den Berg, LH, Van Duijn, CM, Hofman, BA, Uitterlinden, AG, Jhamai, PM, Verbiest, M, Suchiman, HED, Verkerk, M, Van der Breggen, R, Van Rooij, J, Lakenberg, N, Mei, H, Bot, J, Zhernakova, DV, 't Hof, PV, Deelen, P, Nooren, I, Moed, M, Vermaat, M, Luijk, R, Bonder, MJ, Van Iterson, M, Van Dijk, F, Van Galen, M, Arindrarto, W, Swertz, MA, Van Zwet, EW, Isaacs, A, Francioli, LC, Menelaou, A, Pulit, SL, Palamara, PF, Elbers, CC, Neerincx, PB, Ye, K, Guryev, V, Kloosterman, WP, Abdellaoui, A, Van Leeuwen, EM, Van Oven, M, Li, M, Laros, JF, Karssen, LC, Kanterakis, A, Amin, N, Lameijer, EW, Kattenberg, M, Dijkstra, M, Byelas, H, Van Setten, J, Van Schaik, BD, Nijman, IJ, Renkens, I, Marschall, T, Schonhuth, A, Hehir-Kwa, JY, Handsaker, RE, Polak, P, Sohail, M, Vuzman, D, Hormozdiari, F, Van Enckevort, D, Koval, V, Moed, MH, Van der Velde, KJ, Rivadeneira, F, Estrada, K, Medina-Gomez, C, McCarroll, SA, De Craen, AJ, Suchiman, HE, Oostra, B, Willemsen, G, Platteel, M, Pitts, SJ, Potluri, S, Sundar, P, Cox, DR, Sunyaev, SR, Stoneking, M, De Knijff, P, Kayser, M, Li, Q, Li, Y, Du, Y, Chen, R, Cao, H, Li, N, Cao, S, Wang, J, Bovenberg, JA, Pe'er, I, Van Ommen, GJ, De Bakker, PI, Consortium, Bios, Consortium, Gonl, BIOS consortium, GoNL consortium, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology and Data Science, AII - Inflammatory diseases, APH - Methodology, Experimental Immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Personalized Medicine, Biological Psychology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Interne Geneeskunde, RS: CARIM - R3 - Vascular biology, MUMC+: MA Reumatologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Hematologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Endocrinologie (9), MUMC+: HVC Pieken Maastricht Studie (9), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: MA Interne Geneeskunde (3), RS: Carim - B01 Blood proteins & engineering, RS: FHML MaCSBio, RS: CARIM - R1 - Thrombosis and haemostasis, RS: CARIM - R1.01 - Blood proteins & engineering, Biochemie, Psychiatry, VU University medical center, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Internal Medicine, Epidemiology, Genetic Identification, and Clinical Genetics
Subjects: Netherlands Twin Register (NTR), Male, 0301 basic medicine, Receptors, Cytoplasmic and Nuclear/genetics, CHROMOSOME-INACTIVATION, BIOS consortium, Receptors, Cytoplasmic and Nuclear, Septins/genetics, Population genetics, GoNL consortium, Population/genetics, Negative selection, 0302 clinical medicine, X Chromosome Inactivation, Receptors, Non-U.S. Gov't, Genetics (clinical), Netherlands, Genetics & Heredity, Genetics, education.field_of_study, Membrane Glycoproteins, Dosage compensation, DMD LOCUS, Research Support, Non-U.S. Gov't, Receptors, Peptide/genetics, Intracellular Signaling Peptides and Proteins, Peptide/genetics, Single Nucleotide, CARRIERS, TRANSLOCATION, VARIABILITY, Female, Life Sciences & Biomedicine, EXPRESSION, Biochemistry & Molecular Biology, Receptors, Peptide, Population, ADRENOLEUKODYSTROPHY, Biology, Research Support, Polymorphism, Single Nucleotide, Article, X-inactivation, DUCHENNE MUSCULAR-DYSTROPHY, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Journal Article, Humans, Polymorphism, Allele, education, Skewed X-inactivation, Gene, 0604 Genetics, Calcium-Binding Proteins/genetics, Science & Technology, CONSEQUENCES, Calcium-Binding Proteins, Membrane Glycoproteins/genetics, 030104 developmental biology, Cytoplasmic and Nuclear/genetics, PATTERNS, Intracellular Signaling Peptides and Proteins/genetics, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Septins, 030217 neurology & neurosurgery
Abstract: X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants.
Published: 2019

5. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, Andreassen, OA, Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, and Andreassen, OA
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Published: 2021

6. Population-based identity-by-descent mapping combined with exome sequencing to detect rare risk variants for schizophrenia

Author: Harold, D, Connolly, S, Riley, BP, Kendler, KS, McCarthy, SE, McCombie, WR, Richards, A, Owen, MJ, O'Donovan, MC, Walters, J, Donnelly, P, Bates, L, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Hopkins, L, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Ripke, S, Neale, BM, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M-L, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chan, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Lee, J, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Muller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Buxbaum, JD, Borglum, AD, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, Harold, D, Connolly, S, Riley, BP, Kendler, KS, McCarthy, SE, McCombie, WR, Richards, A, Owen, MJ, O'Donovan, MC, Walters, J, Donnelly, P, Bates, L, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Hopkins, L, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Ripke, S, Neale, BM, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M-L, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chan, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Lee, J, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Muller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Buxbaum, JD, Borglum, AD, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, and Sullivan, PF
Abstract: Genome-wide association studies (GWASs) are highly effective at identifying common risk variants for schizophrenia. Rare risk variants are also important contributors to schizophrenia etiology but, with the exception of large copy number variants, are difficult to detect with GWAS. Exome and genome sequencing, which have accelerated the study of rare variants, are expensive so alternative methods are needed to aid detection of rare variants. Here we re-analyze an Irish schizophrenia GWAS dataset (n = 3,473) by performing identity-by-descent (IBD) mapping followed by exome sequencing of individuals identified as sharing risk haplotypes to search for rare risk variants in coding regions. We identified 45 rare haplotypes (>1 cM) that were significantly more common in cases than controls. By exome sequencing 105 haplotype carriers, we investigated these haplotypes for functional coding variants that could be tested for association in independent GWAS samples. We identified one rare missense variant in PCNT but did not find statistical support for an association with schizophrenia in a replication analysis. However, IBD mapping can prioritize both individual samples and genomic regions for follow-up analysis but genome rather than exome sequencing may be more effective at detecting risk variants on rare haplotypes.
Published: 2019

7. Genome-wide association study reveals greater polygenic loading for schizophrenia in cases with a family history of illness

Author: Bigdeli, T. B, Ripke, S, Bacanu, Sa, Lee, S. H, Wray, Nr, Gejman, P. V, Rietschel, M, Cichon, S, St Clair, D, Corvin, A, Kirov, G, Mcquillin, A, Gurling, H, Rujescu, D, Andreassen, O. A, Werge, T, Blackwood, D. H. R, Pato, C. N, Pato, M. T, Malhotra, A. K, O'Donovan, M. C, Kendler, K. S, Fanous, A. H, Neale, Bm, Walters, Jt, Farh, Kh, Holmans, Pa, Lee, P, Bulik Sullivan, B, Collier, Da, Huang, H, Pers, Th, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Begemann, M, Belliveau, Ra, Bene, J, Bergen, Se, Bevilacqua, E, Bigdeli, Tb, Black, Dw, Børglum, Ad, Bruggeman, R, Buccola, Ng, Buckner, Rl, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, Rm, Carr, Vj, Carrera, N, Catts, Sv, Chambert, Kd, Chan, Rc, Chen, Ry, Chen, Ey, Cheng, W, Cheung, Ef, Chong, Sa, Cloninger, C, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, Jj, Curtis, D, Davidson, M, Davis, Kl, Degenhardt, F, Del, Favero, J, Delisi, Le, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott Price, V, Essioux, L, Fanous, Ah, Farrell, Ms, Frank, J, Franke, L, Freedman, R, Freimer, Nb, Friedl, M, Friedman, Ji, Fromer, M, Genovese, G, Georgieva, L, Gershon, Es, Giegling, I, Giusti Rodríguez, P, Godard, S, Goldstein, Ji, Golimbet, V, Gopal, S, Gratten, J, Grove, J, Haan, De, L, Hammer, C, Hamshere, Ml, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, Am, Henskens, Fa, Herms, S, Hirschhorn, Jn, Hoffmann, P, Hofman, A, Hollegaard, Mv, Hougaard, Dm, Ikeda, M, Joa, I, Julìa, A, Kahn, Rs, Kalaydjieva, L, Karachanak Yankova, S, Karjalainen, J, Kavanagh, D, Keller, Mc, Kelly, Bj, Kennedy, Jl, Khrunin, A, Kim, Y, Klovins, J, Knowles, Ja, Konte, B, Kucinskas, V, Kucinskiene, Za, Kuzelova Ptackova, H, Kähler, Ak, Laurent, C, Keong, Jl, Lee, S, Legge, Se, Lerer, B, Li, M, Li, T, Liang, Ky, Lieberman, J, Limborska, S, Loughland, Cm, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, Pk, Maher, Bs, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, Mccarley, Rw, Mcdonald, C, Mcintosh, Am, Meier, S, Meijer, Cj, Melegh, B, Melle, I, Mesholam Gately, Ri, Metspalu, A, Michie, Pt, Milani, L, Milanova, V, Mokrab, Y, Morris, Dw, Mors, O, Mortensen, Pb, Murphy, Kc, Murray, Rm, Myin Germeys, I, Müller Myhsok, B, Nelis, M, Nenadic, I, Nertney, Da, Nestadt, G, Nicodemus, Kk, Nikitina Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, F, Sy, Oh, Olincy, A, Olsen, L, Jv, Os, Pantelis, C, Papadimitriou, Gn, Papiol, S, Parkhomenko, E, Pato, Mt, Paunio, T, Pejovic Milovancevic, M, Perkins, Do, Pietiläinen, O, Pimm, J, Pocklington, Aj, Powell, J, Price, A, Pulver, Ae, Purcell, Sm, Quested, D, Rasmussen, Hb, Reichenberg, A, Reimers, Ma, Richards, Al, Roffman, Jl, Roussos, P, Ruderfer, Dm, Salomaa, V, Sanders, Ar, Schall, U, Schubert, Cr, Schulze, Tg, Schwab, Sg, Scolnick, Em, Scott, Rj, Seidman, Lj, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, Jm, Sim, K, Slominsky, P, Smoller, Jw, Hc, So, Spencer, Cc, Stahl, Ea, Stefansson, H, Steinberg, S, Stogmann, E, Straub, Re, Strengman, E, Strohmaier, J, Stroup, T, Subramaniam, M, Suvisaari, J, Svrakic, Dm, Szatkiewicz, Jp, Söderman, E, Thirumalai, S, Toncheva, D, Tooney, Pa, Tosato, Sarah, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, Bt, Weiser, M, Wildenauer, Db, Williams, Nm, Williams, S, Witt, Sh, Wolen, Ar, Wong, Eh, Wormley, Bk, Jq, Wu, Hs, Xi, Zai, Cc, Zheng, X, Zimprich, F, Stefansson, K, Visscher, Pm, Adolfsson, R, Andreassen, Oa, Blackwood, Dh, Bramon, E, Buxbaum, Jd, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, Pv, Gill, M, Hultman, Cm, Iwata, N, Jablensky, Av, Jönsson, Eg, Kendler, Ks, Knight, J, Lencz, T, Levinson, Df, Qs, Li, Liu, J, Malhotra, Ak, Mccarroll, Sa, Moran, Jl, Mowry, Bj, Nöthen, Mm, Ophoff, Ra, Owen, Mj, Palotie, A, Pato, Cn, Petryshen, Tl, Posthuma, D, Riley, Bp, Sham, Pc, Sklar, P, Clair, Ds, Weinberger, Dr, Wendland, Jr, Daly, Mj, Sullivan, Pf, O'Donovan, Mc, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Bigdeli, Tim B, Ripke, Stephan, Bacanu, Silviu-Alin, Lee, Sang Hong, Fanous, Ayman H, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Psychosis Endophenotype International Consortium, Wellcome Trust Case-Control Consortium 2, Other departments, Adult Psychiatry, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and Del-Favero, Jurgen
Subjects: 0301 basic medicine, Multifactorial Inheritance, Bipolar Disorder, Inheritance Patterns, Genome-wide association study, Single-nucleotide polymorphism, polygenic, heritability, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, Humans, SNP, GWAS, Family, Genetic Predisposition to Disease, Family history, Allele, Genetics (clinical), Genetic association, Genetics & Heredity, Psychiatry, Genetics, Depressive Disorder, Major, family history, Models, Genetic, Case-control study, medicine.disease, 3. Good health, schizophrenia, Psychiatry and Mental health, 030104 developmental biology, Schizophrenia, Case-Control Studies, Human medicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N=978), cases reporting no such family history (N=4,503), and unscreened controls (N=8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R-2=0.0021; P=0.00331; P-value threshold
Published: 2016

8. Age at first birth in women is genetically associated with increased risk of schizophrenia

Author: Ni, G, Gratten, J, Wray, NR, Lee, SH, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Haan, L de, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Juliá, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kähler, AK, Laurent, C, Keong, JLC, Legge, SE, Lerer, B, Li, M, Li, T, Liang, KY, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Müller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, SY, Olincy, A, Olsen, L, van Os, JV, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietiläinen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, HC, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Söderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, Xuebin, Zimprich, F, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Børglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, Daniëlle, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Clair, DS, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, O'Donovan, MC, Ni, G, Gratten, J, Wray, NR, Lee, SH, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Haan, L de, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Juliá, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kähler, AK, Laurent, C, Keong, JLC, Legge, SE, Lerer, B, Li, M, Li, T, Liang, KY, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lönnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Müller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, SY, Olincy, A, Olsen, L, van Os, JV, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietiläinen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, HC, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Söderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, Xuebin, Zimprich, F, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Børglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jönsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Nöthen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, Daniëlle, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Clair, DS, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, and O'Donovan, MC
Published: 2018

9. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases

Author: Gusev, A, Lee, Sh, SWE SCZ, Consortium, O'Dushlaine, Cgusev, Trynka, G, Finucane, H, Vilhjálmsson, Bj, Xu, H, Zang, C, Ripke, S, Bulik Sullivan, B, Stahl, E, Schizophrenia, Working, Neale, Bm, Corvin, A, Walters, Jt, Farh, Kh, Holmans, Pa, Lee, P, Collier, Da, Huang, H, Pers, Th, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, Sa, Begemann, M, Belliveau, Ra, Bene, J, Bergen, Se, Bevilacqua, E, Bigdeli, Tb, Black, Dw, Børglum, Ad, Bruggeman, R, Buccola, Ng, Buckner, Rl, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, Rm, Carr, Vj, Carrera, N, Catts, Sv, Chambert, Kd, Chan, Rc, Chen, Ry, Chen, Ey, Cheng, W, Cheung, Ef, Chong, Sa, Cloninger, Cr, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, Jj, Curtis, D, Davidson, M, Davis, Kl, Degenhardt, F, Del, Favero, Delisi, Le, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott Price, V, Essioux, L, Fanous, Ah, Farrell, Ms, Frank, J, Franke, L, Freedman, R, Freimer, Nb, Friedl, M, Friedman, Ji, Fromer, M, Genovese, G, Georgieva, L, Gershon, Es, Giegling, I, Giusti Rodrguez, P, Godard, S, Goldstein, Ji, Golimbet, V, Gopal, S, Gratten, J, Grove, J, Haan, De, Hammer, C, Hamshere, Ml, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, Am, Henskens, Fa, Herms, S, Hirschhorn, Jn, Hoffmann, P, Hofman, A, Hollegaard, Mv, Hougaard, Dm, Ikeda, M, Joa, I, Julià, A, Kahn, Rs, Kalaydjieva, L, Karachanak Yankova, S, Karjalainen, J, Kavanagh, D, Keller, Mc, Kelly, Bj, Kennedy, Jl, Khrunin, A, Kim, Y, Klovins, J, Knowles, Ja, Konte, B, Kucinskas, V, Kucinskiene, Za, Kuzelova Ptackova, H, Kähler, Ak, Laurent, C, Keong, Jl, Legge, Se, Lerer, B, Li, M, Li, T, Liang, Ky, Lieberman, J, Limborska, S, Loughland, Cm, Lubinski, J, Lnnqvist, J, Macek, M, Magnusson, Pk, Maher, Bs, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, Mccarley, Rw, Mcdonald, C, Mcintosh, Am, Meier, S, Meijer, Cj, Melegh, B, Melle, I, Mesholam Gately, Ri, Metspalu, A, Michie, Pt, Milani, L, Milanova, V, Mokrab, Y, Morris, Dw, Mors, O, Mortensen, Pb, Murphy, Kc, Murray, Rm, Myin Germeys, I, Mller Myhsok, B, Nelis, M, Nenadic, I, Nertney, Da, Nestadt, G, Nicodemus, Kk, Nikitina Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, Fa, Sy, Oh, Olincy, A, Olsen, L, Van, Os, Pantelis, C, Papadimitriou, Gn, Papiol, S, Parkhomenko, E, Pato, Mt, Paunio, T, Pejovic Milovancevic, M, Perkins, Do, Pietilinen, O, Pimm, J, Pocklington, Aj, Powell, J, Price, A, Pulver, Ae, Purcell, Sm, Quested, D, Rasmussen, Hb, Reichenberg, A, Reimers, Ma, Richards, Al, Roffman, Jl, Roussos, P, Ruderfer, Dm, Salomaa, V, Sanders, Ar, Schall, U, Schubert, Cr, Schulze, Tg, Schwab, Sg, Scolnick, Em, Scott, Rj, Seidman, Lj, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, Jm, Sim, K, Slominsky, P, Smoller, Jw, Hc, So, Spencer, Cc, Stahl, Ea, Stefansson, H, Steinberg, S, Stogmann, E, Straub, Re, Strengman, E, Strohmaier, J, Stroup, Ts, Subramaniam, M, Suvisaari, J, Svrakic, Dm, Szatkiewicz, Jp, Sderman, E, Thirumalai, S, Toncheva, D, Tooney, Pa, Tosato, Sarah, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, Bt, Weiser, M, Wildenauer, Db, Williams, Nm, Williams, S, Witt, Sh, Wolen, Ar, Wong, Eh, Wormley, Bk, Jq, Wu, Hs, Xi, Zai, Cc, Zheng, X, Zimprich, F, Wray, Nr, Stefansson, K, Visscher, Pm, Adolfsson, R, Andreassen, Oa, Blackwood, Dh, Bramon, E, Buxbaum, Jd, Brglum, Ad, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, Pv, Gill, M, Gurling, H, Hultman, Cm, Iwata, N, Jablensky, Av, Jönsson, Eg, Kendler, Ks, Kirov, G, Knight, J, Lencz, T, Levinson, Df, Qs, Li, Liu, J, Malhotra, Ak, Mccarroll, Sa, Mcquillin, A, Moran, Jl, Mowry, Bj, Nthen, Mm, Ophoff, Ra, Owen, Mj, Palotie, A, Pato, Cn, Petryshen, Tl, Posthuma, D, Rietschel, M, Riley, Bp, Rujescu, D, Sham, Pc, Sklar, P, Clair, St, Weinberger, Dr, Wendland, Jr, Werge, T, Daly, Mj, Sullivan, Pf, O'Donovan, Mc, Chambert, K, Akterin, S, Bergen, S, Ruderfer, D, Scolnick, E, Purcell, S, Mccarroll, S, Daly, M, Pasaniuc, B, Raychaudhuri, S, Price, Al, Gusev, Alexander, Lee, S Hong, Trynka, Gosia, Finucane, Hilary K, Price, Alkes L, Schizophrenia Working Group of the Psychiatric Genomics Consortium, SWE-SCZ Consortium, ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Complex Trait Genetics, Functional Genomics, and Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease
Subjects: Linkage disequilibrium, GWAS, schizophrenia, SNP, trait heritability, disease architecture, Inheritance Patterns, Single-nucleotide polymorphism, Genome-wide association study, Biology, Article, Open Reading Frames, SDG 3 - Good Health and Well-being, Genetic, Models, Genotype, Genetics, Humans, Genetics(clinical), Computer Simulation, Regulatory Elements, Transcriptional, Exome, Genetics (clinical), genotype imputation, Genetic association, Genetics & Heredity, genome-wide association study, Models, Genetic, Genetic Diseases, Inborn, Genetic Variation, Heritability, exome chips, Regulatory Elements, Inborn, Genetic Diseases, Transcriptional, coding variants, Genome-Wide Association Study
Abstract: Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (h(g)(2)) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of h(g)(2) from imputed SNPs (5.1 x enrichment; p = 3.7 x 10(-17)) and 38% (SE = 4%) of h(g)(2) from genotyped SNPs (1.6 x enrichment, p = 1.0 x 10(-4)). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained
Published: 2014

10. Genetic influences on schizophrenia and subcortical brain volumes: Large-scale proof of concept

Author: Franke, B, van Hulzen, KJE, Arias-Vasquez, A, Bralten, J, Hoogman, M, Klein, M, van Donkelaar, MMJ, Hakobjan, MMH, Heister, AJGAM, Makkinje, RRR, Naber, MAM, van der Marel, SSL, Mostert, JC, Brunner, HG, van Bokhoven, H, Zwiers, MP, Buitelaar, JK, Fernández, G, Fisher, SE, Francks, C, Stein, JL, Hibar, DP, Thompson, PM, Ripke, S, Anttila, V, Neale, BM, Farh, KH, Bulik-Sullivan, B, Huang, H, Fromer, M, Goldstein, JI, Daly, MJ, Walters, RK, Smoller, JW, Lee, P, Belliveau, RA, Bergen, SE, Bevilacqua, E, Chambert, KD, Genovese, G, O'Dushlaine, C, Scolnick, EM, McCarroll, SA, Moran, JL, Palotie, A, Petryshen, TL, Erk, S, Heinz, A, Mohnke, S, Romanczuk-Seiferth, N, Walter, H, DeLisi, LE, McCarley, RW, Mesholam-Gately, RI, Seidman, LJ, Nichols, TE, Neale, MC, McIntosh, AM, Papmeyer, M, Sprooten, E, Lawrie, SM, Sussmann, JE, McMahon, FJ, Yao, Y, Meyer-Lindenberg, A, Schwarz, E, Grimm, O, Mattheisen, M, Agerbo, E, Demontis, D, Hansen, T, Mors, O, Olsen, L, Rasmussen, HB, Børglum, AD, Mortensen, PB, Werge, T, Andreassen, OA, Brown, AA, Athanasiu, L, Hartberg, CB, Haukvik, U, Melle, I, Gruber, O, Kraemer, B, Keil, M, Sachdev, PS, Mather, KA, Thalamuthu, A, Armstrong, NJ, Assareh, AA, Brodaty, H, Reppermund, S, Wen, W, Roiz-Santiañez, R, Perez-Iglesias, R, Saykin, AJ, Kim, S, Nho, K, Risacher, SL, Franke, B, van Hulzen, KJE, Arias-Vasquez, A, Bralten, J, Hoogman, M, Klein, M, van Donkelaar, MMJ, Hakobjan, MMH, Heister, AJGAM, Makkinje, RRR, Naber, MAM, van der Marel, SSL, Mostert, JC, Brunner, HG, van Bokhoven, H, Zwiers, MP, Buitelaar, JK, Fernández, G, Fisher, SE, Francks, C, Stein, JL, Hibar, DP, Thompson, PM, Ripke, S, Anttila, V, Neale, BM, Farh, KH, Bulik-Sullivan, B, Huang, H, Fromer, M, Goldstein, JI, Daly, MJ, Walters, RK, Smoller, JW, Lee, P, Belliveau, RA, Bergen, SE, Bevilacqua, E, Chambert, KD, Genovese, G, O'Dushlaine, C, Scolnick, EM, McCarroll, SA, Moran, JL, Palotie, A, Petryshen, TL, Erk, S, Heinz, A, Mohnke, S, Romanczuk-Seiferth, N, Walter, H, DeLisi, LE, McCarley, RW, Mesholam-Gately, RI, Seidman, LJ, Nichols, TE, Neale, MC, McIntosh, AM, Papmeyer, M, Sprooten, E, Lawrie, SM, Sussmann, JE, McMahon, FJ, Yao, Y, Meyer-Lindenberg, A, Schwarz, E, Grimm, O, Mattheisen, M, Agerbo, E, Demontis, D, Hansen, T, Mors, O, Olsen, L, Rasmussen, HB, Børglum, AD, Mortensen, PB, Werge, T, Andreassen, OA, Brown, AA, Athanasiu, L, Hartberg, CB, Haukvik, U, Melle, I, Gruber, O, Kraemer, B, Keil, M, Sachdev, PS, Mather, KA, Thalamuthu, A, Armstrong, NJ, Assareh, AA, Brodaty, H, Reppermund, S, Wen, W, Roiz-Santiañez, R, Perez-Iglesias, R, Saykin, AJ, Kim, S, Nho, K, and Risacher, SL
Abstract: Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.
Published: 2016

11. Schizophrenia risk from complex variation of complement component 4

Author: Sekar, A, Bialas, AR, de Rivera, H, Davis, A, Hammond, TR, Kamitaki, N, Tooley, K, Presumey, J, Baum, M, Van Doren, V, Genovese, G, Rose, SA, Handsaker, RE, Daly, MJ, Carroll, MC, Stevens, B, McCarroll, SA, Sekar, A, Bialas, AR, de Rivera, H, Davis, A, Hammond, TR, Kamitaki, N, Tooley, K, Presumey, J, Baum, M, Van Doren, V, Genovese, G, Rose, SA, Handsaker, RE, Daly, MJ, Carroll, MC, Stevens, B, and McCarroll, SA
Abstract: Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.
Published: 2016

12. The Lin28/let-7 axis regulates glucose metabolism

Author: Zhu H, Shyh Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, DIAGRAM Consortium, MAGIC Investigators, Altshuler D, Daley G.Q. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia Naji N, Mägi R, Randall J, Johnson T, Elliott P, Rybin D, Henneman P, Dehghan A, Hottenga JJ, Song K, Goel A, Egan JM, Lajunen T, Doney A, Voight BF, Kanoni S, Cavalcanti Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Crisponi L, Day IN, de Geus EJ, Delplanque J, Fedson AC, Fischer Rosinsky A, Forouhi NG, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen AL, Hayward C, Heath SC, Hercberg S, Hicks AA, Hillman DR, Hingorani AD, Hui J, Hung J, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Manning AK, Martínez Larrad MT, McAteer JB, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Mukherjee S, Naitza S, Neville MJ, Oostra BA, Orrù M, Pakyz R, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rice K, Ripatti S, Rivadeneira F, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Seedorf U, Sharp SJ, Shields B, Sigurðsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Tönjes A, Uitterlinden AG, van Dijk KW, Varma D, Visvikis Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Ward KL, Watkins H, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano Ríos M, Lind L, Palmer LJ, Franks PW, Ebrahim S, Marmot M, Wright AF, Stumvoll M, Hamsten A, Buchanan TA, Valle TT, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Ferrucci L, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Barroso I., PAOLISSO, Giuseppe, Zhu, H, Shyh Chang, N, Segrè, Av, Shinoda, G, Shah, Sp, Einhorn, W, Takeuchi, A, Engreitz, Jm, Hagan, Jp, Kharas, Mg, Urbach, A, Thornton, Je, Triboulet, R, Gregory, Ri, Diagram, Consortium, Magic, Investigator, Altshuler, D, Voight BF, Daley G. Q., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Voight, Bf, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, and Barroso, I.
Published: 2011

13. Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Author: Ripke, S, O'Dushlaine, C, Chambert, K, Moran, Jl, Kähler, Ak, Akterin, S, Bergen, Se, Collins, Al, Crowley, Jj, Fromer, M, Kim, Y, Lee, Sh, Magnusson, Pk, Sanchez, N, Stahl, Ea, Williams, S, Wray, Nr, Xia, K, Bettella, F, Borglum, Ad, Bulik Sullivan, Bk, Cormican, P, Craddock, N, Leeuw, De, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, Ml, Holmans, P, Hougaard, Dm, Kendler, Ks, Lin, K, Morris, Dw, Mors, O, Mortensen, Pb, Neale, Bm, O'Neill, Fa, Owen, Mj, Milovancevic, Mp, Posthuma, D, Powell, J, Richards, Al, Riley, Bp, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, Ab, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, Sarah, Verhage, M, Walters, Jt, Multicenter Genetic Studies of Schizophrenia Consortium, Levinson, Df, Gejman, Pv, Laurent, C, Mowry, Bj, O'Donovan, Mc, Pulver, Ae, Schwab, Sg, Wildenauer, Db, Dudbridge, F, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, Fb, Liang, Ky, Maier, W, Mallet, J, Nertney, Da, Nestadt, G, Norton, N, Papadimitriou, Gn, Ribble, R, Sanders, Ar, Silverman, Jm, Walsh, D, Williams, Nm, Wormley, B, Psychosis Endophenotypes International Consortium, Arranz, Mj, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, Rs, Kalaydjieva, L, Lawrie, S, Lewis, Cm, Linszen, Dh, Mata, I, Mcintosh, A, Murray, Rm, Ophoff, Ra, Van, Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Wellcome Trust Case Control Consortium 2, Donnelly, P, Barroso, I, Blackwell, Jm, Brown, Ma, Casas, Jp, Corvin, Ap, Deloukas, P, Duncanson, A, Jankowski, J, Markus, Hs, Mathew, Cg, Palmer, Cn, Plomin, R, Rautanen, A, Sawcer, Sj, Trembath, Rc, Viswanathan, Ac, Wood, Nw, Spencer, Cc, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, Rd, Strange, A, Su, Z, Vukcevic, D, Langford, C, Hunt, Se, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, Sj, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, Ot, Liddle, J, Potter, Sc, Ravindrarajah, R, Ricketts, M, Tashakkori Ghanbaria, A, Waller, Mj, Weston, P, Widaa, S, Whittaker, P, Mccarthy, Mi, Stefansson, K, Scolnick, E, Purcell, S, Mccarroll, Sa, Sklar, P, Hultman, Cm, Sullivan, P. F., Functional Genomics, Molecular and Cellular Neurobiology, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Adult Psychiatry, Ripke, Stephan, O'Dushlaine, Colm, Chambert, Kimberly, Moran, Jennifer L, Lee, Sang Hong, Sullivan, Patrick F, Multicenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2, Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway Icahn Sch Med Mt Sinai, Dept Psychiat, Div Psychiat Genom, New York, NY USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA deCODE Genet, Reykjavik, Iceland Aarhus Univ Hosp, Risskov, Denmark Aarhus Univ, Ctr Integrat Sequencing iSEQ, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Copenhagen, Denmark Univ Dublin Trinity Coll, Dept Psychiat, Dublin 2, Ireland Cardiff Univ, Sch Med, Ctr Psychiat Genet & Genom, MRC, Cardiff CF10 3AX, S Glam, Wales Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Amsterdam, Netherlands Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands Radboud Univ Nijmegen, Inst Comp & Informat Sci, NL-6525 ED Nijmegen, Netherlands Univ Clin Psychiat, Dept Child & Adolescent Psychiat, Skopje, Macedonia Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dublin 2, Ireland Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia Statens Serum Inst, DK-2300 Copenhagen, Denmark Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA Kings Coll London, Inst Psychiat, London, England Aarhus Univ Hosp, Ctr Psychiat Res, Risskov, Denmark Aarhus Univ, Natl Ctr Register Based Res, Aarhus, DenmarkQueens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Belgrade, Fac Med, Belgrade, Serbia Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands Kings Coll London, Dept Neurosci, London, England Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA USA Univ Halle, Dept Psychiat, Halle, Germany Univ Munich, Dept Psychiat, D-80539 Munich, Germany Univ Iceland, Dept Psychiat, Reykjavik, Iceland Landspitali University Hospital Reykjavik, Iceland Tbilisi State Univ, Dept Psychiat, GE-380086 Tbilisi, Rep of Georgia Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands Vrije Univ Amsterdam, Dept Mol & Cellular Neurosci, Amsterdam, Netherlands Natl Inst Hlth & Welf, Mental Hlth & Subst Abuse Serv, Helsinki, Finland Univ Verona, Sect Psychiat, I-37100 Verona, Italy UCL, Inst Cognit Neurosci, London, England UCL, Mental Hlth Sci Unit, London, England Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA Harvard Univ, Sch Med, Dept Genet, Boston, MA USA, Child and Adolescent Psychiatry / Psychology, Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, Human genetics, NCA - Brain mechanisms in health and disease, and NCA - Neurobiology of mental health
Subjects: Male, Candidate gene, SNP, Single-nucleotide polymorphism, Genome-wide association study, Disease, Biology, heritability, neuronal calcium signaling, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Genetics, medicine, Humans, GWAS, Genetic Predisposition to Disease, Bipolar disorder, 030304 developmental biology, Genetic association, Sweden, Genetics & Heredity, 0303 health sciences, medicine.disease, 3. Good health, genome sequencing, schizophrenia, Schizophrenia, Meta-analysis, Case-Control Studies, genetic variation, Female, genome-wide scan, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder. NIMH R01 MH077139 R01 MH095034 Stanley Center for Psychiatric Research Sylvan Herman Foundation Friedman Brain Institute at the Mount Sinai School of Medicine Karolinska Institutet, Karolinska University Hospital Swedish Research Council Swedish County Council Soderstrom Konigska Foundation Netherlands Scientific Organization NWO 645-000-003 info:eu-repo/grantAgreement/EC/FP7/223423 Danish Strategic Research Council H. Lundbeck A/S Faculty of Health Sciences at Aarhus University Lundbeck Foundation Stanley Research Foundation Wellcome Trust 085475/B/08/Z 085475/Z/08/Z
Published: 2013

14. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

Author: den Hoed, M, Eijgelsheim, M, Esko, T, Brundel, Bj, Peal, Ds, Evans, Dm, Nolte, Im, Segrè, Av, Holm, H, Handsaker, Re, Westra, Hj, Johnson, T, Isaacs, A, Yang, J, Lundby, A, Zhao, Jh, Kim, Yj, Go, Mj, Almgren, P, Bochud, M, Boucher, G, Cornelis, Mc, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, Au, Kutalik, Z, Luan, J, Kemp, Jp, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, Me, Njajou, Ot, O'Reilly, Pf, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, Nj, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, Hh, Feitosa, Mf, Kerr, Kf, Lind, Pa, Mihailov, E, Onland Moret NC, Song, C, Weedon, Mn, Xie, W, Yengo, L, Absher, D, Albert, Cm, Alonso, A, Arking, De, de Bakker PI, Balkau, B, Barlassina, C, Benaglio, P, Bis, Jc, Bouatia Naji, N, Brage, S, Chanock, Sj, Chines, Ps, Chung, M, Darbar, D, Dina, C, Dörr, M, Elliott, P, Felix, Sb, Fischer, K, Fuchsberger, C, de Geus EJ, Goyette, P, Gudnason, V, Harris, Tb, Hartikainen, Al, Havulinna, As, Heckbert, Sr, Hicks, Aa, Hofman, A, Holewijn, S, Hoogstra Berends, F, Hottenga, Jj, Jensen, Mk, Johansson, A, Junttila, J, Kääb, S, Kanon, B, Ketkar, S, Khaw, Kt, Knowles, Jw, Kooner, As, Kors, Ja, Kumari, M, Milani, L, Laiho, P, Lakatta, Eg, Langenberg, C, Leusink, M, Liu, Y, Luben, Rn, Lunetta, Kl, Lynch, Sn, Markus, Mr, Marques Vidal, P, Mateo Leach, I, Mcardle, Wl, Mccarroll, Sa, Medland, Se, Miller, Ka, Montgomery, Gw, Morrison, Ac, Müller Nurasyid, M, Navarro, P, Nelis, M, O'Connell, Jr, O'Donnell, Cj, Ong, Kk, Newman, Ab, Peters, A, Polasek, O, Pouta, A, Pramstaller, Pp, Psaty, Bm, Rao, Dc, Ring, Sm, Rossin, Ej, Rudan, D, Sanna, S, Scott, Ra, Sehmi, Js, Sharp, S, Shin, Jt, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stewart, C, Stringham, Hm, Tarasov, Kv, Uitterlinden, Ag, Vandenput, L, Hwang, Sj, Whitfield, Jb, Wijmenga, C, Wild, Sh, Willemsen, G, Wilson, Jf, Witteman, Jc, Wong, A, Wong, Q, Jamshidi, Y, Zitting, P, Boer, Jm, Boomsma, Di, Borecki, Ib, van Duijn CM, Ekelund, U, Forouhi, Ng, Froguel, P, Hingorani, A, Ingelsson, E, Kivimaki, M, Kronmal, Ra, Kuh, D, Lind, L, Martin, Ng, Oostra, Ba, Pedersen, Nl, Quertermous, T, Rotter, Ji, van der Schouw YT, Verschuren, Wm, Walker, M, Albanes, D, Arnar, Do, Assimes, Tl, Bandinelli, S, Boehnke, M, de Boer RA, Bouchard, C, Caulfield, Wl, Chambers, Jc, Curhan, G, Cusi, D, Eriksson, J, Ferrucci, L, van Gilst WH, Glorioso, N, de Graaf, J, Groop, L, Gyllensten, U, Hsueh, Wc, Hu, Fb, Huikuri, Hv, Hunter, Dj, Iribarren, C, Isomaa, B, Jarvelin, Mr, Jula, A, Kähönen, M, Kiemeney, La, van der Klauw MM, Kooner, Js, Kraft, P, Iacoviello, Licia, Lehtimäki, T, Lokki, Ml, Mitchell, Bd, Navis, G, Nieminen, Ms, Ohlsson, C, Poulter, Nr, Qi, L, Raitakari, Ot, Rimm, Eb, Rioux, Jd, Rizzi, F, Rudan, I, Salomaa, V, Sever, Ps, Shields, Dc, Shuldiner, Ar, Sinisalo, J, Stanton, Av, Stolk, Rp, Strachan, Dp, Tardif, Jc, Thorsteinsdottir, U, Tuomilehto, J, van Veldhuisen DJ, Virtamo, J, Viikari, J, Vollenweider, P, Waeber, G, Widen, E, Cho, Ys, Olsen, Jv, Visscher, Pm, Willer, C, Franke, L, Global BPgen Consortium, Cardiogram, Consortium, Erdmann, J, Thompson, Jr, PR GWAS Consortium, Pfeufer, A, QRS GWAS Consortium, Sotoodehnia, N, QT IGC Consortium, Newton Cheh, C, CHARGE AF Consortium, Ellinor, Pt, Stricker, Bh, Metspalu, A, Perola, M, Beckmann, Js, Smith, Gd, Stefansson, K, Wareham, Nj, Munroe, Pb, Sibon, Oc, Milan, Dj, Snieder, H, Samani, Nj, Loos, R. J., Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, CHARGE-AF Consortium, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Humane Biologie, Epidemiology, Public Health, Clinical Genetics, Surgery, Medical Informatics, Internal Medicine, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, ICaR - Circulation and metabolism, EMGO - Lifestyle, overweight and diabetes, NCA - Brain imaging technology, ACS - Heart failure & arrhythmias, Physiology, Internal medicine, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Molecular Neuroscience and Ageing Research (MOLAR), and Stem Cell Aging Leukemia and Lymphoma (SALL)
Subjects: Netherlands Twin Register (NTR), Aetiology, screening and detection [ONCOL 5], 030204 cardiovascular system & hematology, Arrhythmias, DISEASE, Sudden cardiac death, PR INTERVAL, 0302 clinical medicine, Gene Frequency, Heart Rate, Arrhythmias, Cardiac/genetics, 0303 health sciences, COMMON VARIANTS, Dilated cardiomyopathy, Atrial fibrillation, Single Nucleotide, Heart Rate/genetics, 3. Good health, DROSOPHILA, LIBRARY, Cardiology, QRS DURATION, Electrical conduction system of the heart, Metabolic Networks and Pathways, rhytm, conduction, gene, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Quantitative Trait Loci, Cardiac/genetics, Biology, Polymorphism, Single Nucleotide, Article, Sick sinus syndrome, Heart Conduction System/physiopathology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Heart Conduction System, Internal medicine, Cardiac conduction, Heart rate, Genetics, medicine, Animals, Humans, GENOME-WIDE ASSOCIATION, Polymorphism, Health aging / healthy living Cardiovascular diseases [IGMD 5], Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, QT INTERVAL, Arrhythmias, Cardiac, ta3121, medicine.disease, Endocrinology, Genetic Loci, Heart failure, ATRIAL-FIBRILLATION, Genome-Wide Association Study
Abstract: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets. © 2013 Nature America, Inc. All rights reserved.
Published: 2013

15. An integrated map of genetic variation from 1,092 human genomes

Author: Altshuler, DM, Durbin, RM, Abecasis, GR, Bentley, DR, Chakravarti, A, Clark, AG, Donnelly, P, Eichler, EE, Flicek, P, Gabriel, SB, Gibbs, RA, Green, ED, Hurles, ME, Knoppers, BM, Korbel, JO, Lander, ES, Lee, C, Lehrach, H, Mardis, ER, Marth, GT, McVean, GA, Nickerson, DA, Schmidt, JP, Sherry, ST, Wang, J, Wilson, RK, Dinh, H, Kovar, C, Lee, S, Lewis, L, Muzny, D, Reid, J, Wang, M, Fang, X, Guo, X, Jian, M, Jiang, H, Jin, X, Li, G, Li, J, Li, Y, Li, Z, Liu, X, Lu, Y, Ma, X, Su, Z, Tai, S, Tang, M, Wang, B, Wang, G, Wu, H, Wu, R, Yin, Y, Zhang, W, Zhao, J, Zhao, M, Zheng, X, Zhou, Y, Gupta, N, Clarke, L, Leinonen, R, Smith, RE, Zheng-Bradley, X, Grocock, R, Humphray, S, James, T, Kingsbury, Z, Sudbrak, R, Albrecht, MW, Amstislavskiy, VS, Borodina, TA, Lienhard, M, Mertes, F, Sultan, M, Timmermann, B, Yaspo, M-L, Fulton, L, Fulton, R, Weinstock, GM, Balasubramaniam, S, Burton, J, Danecek, P, Keane, TM, Kolb-Kokocinski, A, McCarthy, S, Stalker, J, Quail, M, Davies, CJ, Gollub, J, Webster, T, Wong, B, Zhan, Y, Auton, A, Yu, F, Bainbridge, M, Challis, D, Evani, US, Lu, J, Nagaswamy, U, Sabo, A, Wang, Y, Yu, J, Coin, LJM, Fang, L, Li, Q, Lin, H, Liu, B, Luo, R, Qin, N, Shao, H, Xie, Y, Ye, C, Yu, C, Zhang, F, Zheng, H, Zhu, H, Garrison, EP, Kural, D, Lee, W-P, Leong, WF, Ward, AN, Wu, J, Zhang, M, Griffin, L, Hsieh, C-H, Mills, RE, Shi, X, Von Grotthuss, M, Zhang, C, Daly, MJ, DePristo, MA, Banks, E, Bhatia, G, Carneiro, MO, Del Angel, G, Genovese, G, Handsaker, RE, Hartl, C, McCarroll, SA, Nemesh, JC, Poplin, RE, Schaffner, SF, Shakir, K, Yoon, SC, Lihm, J, Makarov, V, Jin, H, Kim, W, Kim, KC, Rausch, T, Beal, K, Cunningham, F, Herrero, J, McLaren, WM, Ritchie, GRS, Gottipati, S, Keinan, A, Rodriguez-Flores, JL, Sabeti, PC, Grossman, SR, Tabrizi, S, Tariyal, R, Cooper, DN, Ball, EV, Stenson, PD, Barnes, B, Bauer, M, Cheetham, RK, Cox, T, Eberle, M, Kahn, S, Murray, L, Peden, J, Shaw, R, Ye, K, Batzer, MA, Konkel, MK, Walker, JA, MacArthur, DG, Lek, M, Herwig, R, Shriver, MD, Bustamante, CD, Byrnes, JK, De la Vega, FM, Gravel, S, Kenny, EE, Kidd, JM, Lacroute, P, Maples, BK, Moreno-Estrada, A, Zakharia, F, Halperin, E, Baran, Y, Craig, DW, Christoforides, A, Homer, N, Izatt, T, Kurdoglu, AA, Sinari, SA, Squire, K, Xiao, C, Sebat, J, Bafna, V, Burchard, EG, Hernandez, RD, Gignoux, CR, Haussler, D, Katzman, SJ, Kent, WJ, Howie, B, Ruiz-Linares, A, Dermitzakis, ET, Lappalainen, T, Devine, SE, Maroo, A, Tallon, LJ, Rosenfeld, JA, Michelson, LP, Kang, HM, Anderson, P, Angius, A, Bigham, A, Blackwell, T, Busonero, F, Cucca, F, Fuchsberger, C, Jones, C, Jun, G, Lyons, R, Maschio, A, Porcu, E, Reinier, F, Sanna, S, Schlessinger, D, Sidore, C, Tan, A, Trost, MK, Awadalla, P, Hodgkinson, A, Lunter, G, Marchini, JL, Myers, S, Churchhouse, C, Delaneau, O, Gupta-Hinch, A, Iqbal, Z, Mathieson, I, Rimmer, A, Xifara, DK, Oleksyk, TK, Fu, Y, Xiong, M, Jorde, L, Witherspoon, D, Xing, J, Browning, BL, Alkan, C, Hajirasouliha, I, Hormozdiari, F, Ko, A, Sudmant, PH, Chen, K, Chinwalla, A, Ding, L, Dooling, D, Koboldt, DC, McLellan, MD, Wallis, JW, Wendl, MC, Zhang, Q, Tyler-Smith, C, Albers, CA, Ayub, Q, Chen, Y, Coffey, AJ, Colonna, V, Huang, N, Jostins, L, Li, H, Scally, A, Walter, K, Xue, Y, Zhang, Y, Gerstein, MB, Abyzov, A, Balasubramanian, S, Chen, J, Clarke, D, Habegger, L, Harmanci, AO, Jin, M, Khurana, E, Mu, XJ, Sisu, C, Degenhardt, J, Stuetz, AM, Church, D, Michaelson, JJ, Ben, B, Lindsay, SJ, Ning, Z, Frankish, A, Harrow, J, Fowler, G, Hale, W, Kalra, D, Barker, J, Kelman, G, Kulesha, E, Radhakrishnan, R, Roa, A, Smirnov, D, Streeter, I, Toneva, I, Vaughan, B, Ananiev, V, Belaia, Z, Beloslyudtsev, D, Bouk, N, Chen, C, Cohen, R, Cook, C, Garner, J, Hefferon, T, Kimelman, M, Liu, C, Lopez, J, Meric, P, O'Sullivan, C, Ostapchuk, Y, Phan, L, Ponomarov, S, Schneider, V, Shekhtman, E, Sirotkin, K, Slotta, D, Zhang, H, Barnes, KC, Beiswanger, C, Cai, H, Cao, H, Gharani, N, Henn, B, Jones, D, Kaye, JS, Kent, A, Kerasidou, A, Mathias, R, Ossorio, PN, Parker, M, Reich, D, Rotimi, CN, Royal, CD, Sandoval, K, Su, Y, Tian, Z, Tishkoff, S, Toji, LH, Via, M, Yang, H, Yang, L, Zhu, J, Bodmer, W, Bedoya, G, Ming, CZ, Yang, G, You, CJ, Peltonen, L, Garcia-Montero, A, Orfao, A, Dutil, J, Martinez-Cruzado, JC, Brooks, LD, Felsenfeld, AL, McEwen, JE, Clemm, NC, Duncanson, A, Dunn, M, Guyer, MS, Peterson, JL, 1000 Genomes Project Consortium, Dermitzakis, Emmanouil, Universitat de Barcelona, Massachusetts Institute of Technology. Department of Biology, Altshuler, David, and Lander, Eric S.
Subjects: Natural selection, LOCI, Genome-wide association study, Evolutionary biology, Continental Population Groups/genetics, Human genetic variation, VARIANTS, Genoma humà, Binding Sites/genetics, 0302 clinical medicine, RARE, Sequence Deletion/genetics, WIDE ASSOCIATION, ddc:576.5, Copy-number variation, MUTATION, Exome sequencing, transcription factor, Conserved Sequence, Human evolution, Sequence Deletion, Genetics, RISK, 0303 health sciences, Multidisciplinary, Continental Population Groups, 1000 Genomes Project Consortium, Genetic analysis, Genomics, Polymorphism, Single Nucleotide/genetics, Research Highlight, 3. Good health, Algorithm, Multidisciplinary Sciences, Genetic Variation/genetics, Map, Science & Technology - Other Topics, Conserved Sequence/genetics, Integrated approach, General Science & Technology, Genetics, Medical, Haplotypes/genetics, Biology, Polymorphism, Single Nucleotide, Evolution, Molecular, 03 medical and health sciences, Genetic variation, Humans, Transcription Factors/metabolism, POPULATION-STRUCTURE, 1000 Genomes Project, Polymorphism, Nucleotide Motifs, Alleles, 030304 developmental biology, COPY NUMBER VARIATION, Science & Technology, Binding Sites, Human genome, Genome, Human, Racial Groups, Genetic Variation, Genetics, Population, Haplotypes, Genome, Human/genetics, untranslated RNA, 030217 neurology & neurosurgery, Transcription Factors, Genome-Wide Association Study
Abstract: By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations., National Institutes of Health (U.S.) (Grant RC2HL102925), National Institutes of Health (U.S.) (Grant U54HG3067)
Published: 2012

16. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis

Author: Stahl, E. A., Wegmann, D., Trynka, G., Gutierrez Achury, J., Do, R., Voight, B. F., Kraft, P., Chen, R., Kallberg, H. J., F. A. S., Replication, D. G., Consortium, M. a., Genetics, M. I., Kathiresan, S., Wijmenga, C., Gregersen, P. K., Alfredsson, L., Siminovitch, K. A., Worthington, J., P. I. W., Raychaudhuri, S., Plenge, R. M., Voight, Bf, Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Fox, Cs, Franklin, Cs, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam RM, van Haeften TW, van Herpt, T, van Vliet Ostaptchouk JV, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, Fs, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, Js, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn CM, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Kathiresan, S, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, Flavio Luciano, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, Ds, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, As, Peltonen, L, Melander, O, Berglund, G, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Purcell, S, Surti, A, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, Gabriel, Sb, Stahl, Ea, Wegmann, D, Trynka, G, Gutierrez achury, J, Do, R, Voight, Bf, Kraft, P, Che, R, Kallberg, H, Kurreeman, F, Diabetes Genetics Replication And Meta analysis Consortium: Myocardial Infarction Genetics, Consortium, Casari, GIORGIO NEVIO, Kathiresan, S, Wijmenga, C, Gregersen, Pk, Alfredsson, L, Siminovitch, Ka, Worthington, J, De Bakker, Pi, Raychaudhuri, S, Plenge, Rm, and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Multifactorial Inheritance, SUSCEPTIBILITY LOCI, GENETIC SUSCEPTIBILITY, Genome-wide association study, Single-nucleotide polymorphism, Disease, HEART-DISEASE, Biology, VARIANTS, Polymorphism, Single Nucleotide, Article, Arthritis, Rheumatoid, COMMON SNPS, Missing heritability problem, MISSING HERITABILITY, Rheumatoid, Genetic model, Genetic predisposition, Diabetes Mellitus, Humans, genetics, Genetic Predisposition to Disease, Human height, Polymorphism, GENOME-WIDE ASSOCIATION, Arthritis, genetics, Bayes Theorem, Cardiovascular Diseases, genetics, Case-Control Studies, Celiac Disease, genetics, Diabetes Mellitus, Type 2, genetics, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genetics, CELIAC-DISEASE, Bayes Theorem, RISK LOCI, Genetic architecture, Celiac Disease, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Genetic Loci, Case-Control Studies, HUMAN HEIGHT, Genome-Wide Association Study
Abstract: The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases.
Published: 2012

17. Erratum: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution (Nature Genetics (2010) 42 (949-960))

Author: Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Steinthorsdottir, V, Thorleifsson, G, Zillikens, MC, Speliotes, EK, Mägi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, J, Vedantam, S, Esko, T, Kilpeläinen, TO, Kutalik, Z, Li, S, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, L, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Estrada, K, Goddard, ME, Lettre, G, Mangino, M, Nyholt, DR, Purcell, S, Vernon Smith, A, Visscher, PM, Yang, J, McCarroll, SA, Nemesh, J, Voight, BF, Absher, D, Amin, N, Aspelund, T, Coin, L, Glazer, NL, Hayward, C, Heard-Costa, NL, Hottenga, J-J, Johansson, A, Johnson, T, Kaakinen, M, Kapur, K, Ketkar, S, Knowles, JW, Kraft, P, Kraja, AT, Lamina, C, Leitzmann, MF, McKnight, B, Morris, AP, Ong, KK, Perry, JRB, Peters, MJ, Polasek, O, Prokopenko, I, Rayner, NW, Ripatti, S, Rivadeneira, F, Robertson, NR, Sanna, S, Sovio, U, Surakka, I, Teumer, A, Van Wingerden, S, Vitart, V, Zhao, JH, Cavalcanti-Proença, C, Chines, PS, Fisher, E, Kulzer, JR, Lecoeur, C, Narisu, N, Sandholt, C, Scott, LJ, Silander, K, Stark, K, Tammesoo, M-L, Teslovich, TM, Timpson, NJ, Watanabe, RM, Welch, R, Chasman, DI, Cooper, MN, Jansson, J-O, Kettunen, J, Lawrence, RW, Pellikka, N, Perola, M, Vandenput, L, Alavere, H, Almgren, P, Atwood, LD, Bennett, AJ, Biffar, R, Bonnycastle, LL, Bornstein, SR, Buchanan, TA, Campbell, H, Day, INM, Dei, M, Dörr, M, Elliott, P, Erdos, MR, Eriksson, JG, Freimer, NB, Fu, M, Gaget, S, Geus, EJC, Gjesing, AP, Grallert, H, Gräßler, J, Groves, CJ, Guiducci, C, Hartikainen, A-L, Hassanali, N, Havulinna, AS, Herzig, K-H, Hicks, AA, Hui, J, Igl, W, Jousilahti, P, Jula, A, Kajantie, E, Kinnunen, L, Kolcic, I, Koskinen, S, Kovacs, P, Kroemer, HK, Krzelj, V, Kuusisto, J, Kvaloy, K, Laitinen, J, Lantieri, O, Lathrop, GM, Lokki, M-L, Luben, RN, Ludwig, B, McArdle, WL, McCarthy, A, Morken, MA, Nelis, M, Neville, MJ, Paré, G, Parker, AN, Peden, JF, Pichler, I, Pietiläinen, KH, Platou, CGP, Pouta, A, Ridderstråle, M, Samani, NJ, Saramies, J, Sinisalo, J, Smit, JH, Strawbridge, RJ, Stringham, HM, Swift, AJ, Teder-Laving, M, Thomson, B, Usala, G, Van Meurs, JBJ, Van Ommen, G-J, Vatin, V, Volpato, CB, Wallaschofski, H, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Witte, DR, Zgaga, L, Zitting, P, Beilby, JP, James, AL, Kähönen, M, Lehtimäki, T, Nieminen, MS, Ohlsson, C, Palmer, LJ, Raitakari, O, Ridker, PM, Stumvoll, M, Tönjes, A, Viikari, J, Balkau, B, Ben-Shlomo, Y, Bergman, RN, Boeing, H, Smith, GD, Ebrahim, S, Froguel, P, Hansen, T, Hengstenberg, C, Hveem, K, Isomaa, B, Jørgensen, T, Karpe, F, Khaw, K-T, Laakso, M, Lawlor, DA, Marre, M, Meitinger, T, Metspalu, A, Midthjell, K, Pedersen, O, Salomaa, V, Schwarz, PEH, Tuomi, T, Tuomilehto, J, Valle, TT, Wareham, NJ, Arnold, AM, Beckmann, JS, Bergmann, S, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Collins, FS, Eiriksdottir, G, Gudnason, V, Gyllensten, U, Hamsten, A, Hattersley, AT, Hofman, A, Hu, FB, Illig, T, Iribarren, C, Jarvelin, M-R, Kao, WHL, Kaprio, J, Launer, LJ, Munroe, PB, Oostra, B, Penninx, BW, Pramstaller, PP, Psaty, BM, Quertermous, T, Rissanen, A, Rudan, I, Shuldiner, AR, Soranzo, N, Spector, TD, Syvanen, A-C, Uda, M, Uitterlinden, A, Völzke, H, Vollenweider, P, Wilson, JF, Witteman, JC, Wright, AF, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Frayling, TM, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, North, KE, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, Hirschhorn, JN, Assimes, TL, Wichmann, H-E, Thorsteinsdottir, U, Van Duijn, CM, Stefansson, K, Cupples, LA, Loos, RJF, Barroso, I, McCarthy, MI, Fox, CS, Mohlke, KL, and Lindgren, CM
Published: 2011

18. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author: Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, Bouatia Naji, N, Dimas, As, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, Cs, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, Kerr Conte, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, Martínez Larrad MT, Narisu, N, Nastase Mannila, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, van 't Hooft FM, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, Serrano Ríos, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, Fs, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, Voight BF, Florez J. C., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, Mulic, R, Ngwa, Js, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, Ms, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, Ds, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, Is, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, Ms, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, Js, Boeing, H, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository
Subjects: Male, Netherlands Twin Register (NTR), endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medizin, Genome-wide association study, Type 2 diabetes, CORONARY HEART-DISEASE, Fasting/blood, 0302 clinical medicine, Insulin, Glucose homeostasis, ddc:576.5, Genome-wide, Diabetes Mellitus, Type 2/blood/genetics/metabolism, CARDIoGRAM Consortium, POPULATION, Proinsulin, RISK, Genetics, 0303 health sciences, INSULIN SENSITIVITY, 11 Medical And Health Sciences, Fasting, Polymorphism, Single Nucleotide/genetics, OBESITY, Female, type 2 diabetes, Life Sciences & Biomedicine, hormones, hormone substitutes, and hormone antagonists, Insulin processing, Adult, medicine.medical_specialty, endocrine system, ENDOCRINOLOGY & METABOLISM, SUSCEPTIBILITY LOCI, Genotype, 030209 endocrinology & metabolism, DIAGRAM Consortium, Biology, C4D Consortium, Polymorphism, Single Nucleotide, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Insulin resistance, BETA-CELL FUNCTION, SDG 3 - Good Health and Well-being, Internal medicine, GIANT Consortium, Internal Medicine, medicine, Humans, METAANALYSIS, 030304 developmental biology, Science & Technology, Genome, Human, Hormonal regulation [IGMD 6], Genetic Variation, nutritional and metabolic diseases, proinsulin, medicine.disease, Proinsulin/blood, TCF7L2, Endocrinology, Diabetes Mellitus, Type 2, MuTHER Consortium, GLUCOSE-HOMEOSTASIS, Insulin/blood
Abstract: OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.
Published: 2011

19. Erratum: New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (Nature Genetics (2010) 42 (105-116))

Author: Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Mägi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparsø, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proença, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, De Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jørgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martínez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orr, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigursson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvänen, A-C, Tanaka, T, Thorand, B, Tichet, J, Tönjes, A, Tuomi, T, Uitterlinden, AG, Van Dijk, KW, Van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Consortium, D, Consortium, G, Consortium, GB, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Ríos, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Hamsten, A, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, Van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, and Barroso, I
Published: 2010

20. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk (vol 42, pg 105, 2010)

Author: Dupuis, J, Langenberg, C, Prokopenko, I, Saxena, R, Soranzo, N, Jackson, AU, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Gloyn, AL, Lindgren, CM, Maegi, R, Morris, AP, Randall, J, Johnson, T, Elliott, P, Rybin, D, Thorleifsson, G, Steinthorsdottir, V, Henneman, P, Grallert, H, Dehghan, A, Hottenga, JJ, Franklin, CS, Navarro, P, Song, K, Goel, A, Perry, JRB, Egan, JM, Lajunen, T, Grarup, N, Sparso, T, Doney, A, Voight, BF, Stringham, HM, Li, M, Kanoni, S, Shrader, P, Cavalcanti-Proenca, C, Kumari, M, Qi, L, Timpson, NJ, Gieger, C, Zabena, C, Rocheleau, G, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, McCarroll, SA, Payne, F, Roccasecca, RM, Pattou, F, Sethupathy, P, Ardlie, K, Ariyurek, Y, Balkau, B, Barter, P, Beilby, JP, Ben-Shlomo, Y, Benediktsson, R, Bennett, AJ, Bergmann, S, Bochud, M, Boerwinkle, E, Bonnefond, A, Bonnycastle, LL, Borch-Johnsen, K, Boettcher, Y, Brunner, E, Bumpstead, SJ, Charpentier, G, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Cornelis, M, Crawford, G, Crisponi, L, Day, INM, de Geus, EJC, Delplanque, J, Dina, C, Erdos, MR, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Fox, CS, Frants, R, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Groves, CJ, Grundy, S, Gwilliam, R, Gyllensten, U, Hadjadj, S, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hassanali, N, Hayward, C, Heath, SC, Hercberg, S, Herder, C, Hicks, AA, Hillman, DR, Hingorani, AD, Hofman, A, Hui, J, Hung, J, Isomaa, B, Johnson, PRV, Jorgensen, T, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, YA, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, GM, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Lyssenko, V, Mahley, R, Mangino, M, Manning, AK, Martinez-Larrad, MT, McAteer, JB, McCulloch, LJ, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Morken, MA, Mukherjee, S, Naitza, S, Narisu, N, Neville, MJ, Oostra, BA, Orru, M, Pakyz, R, Palmer, CNA, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Perola, M, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Psaty, BM, Rathmann, W, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Roden, M, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Scott, LJ, Seedorf, U, Sharp, SJ, Shields, B, Sigurosson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvaenen, A-C, Tanaka, T, Thorand, B, Tichet, J, Toenjes, A, Tuomi, T, Uitterlinden, AG, van Dijk, KW, van Hoek, M, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Walters, GB, Ward, KL, Watkins, H, Weedon, MN, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zeggini, E, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, MC, Borecki, IB, Loos, RJF, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Hattersley, AT, Silander, K, Salomaa, V, Smith, GD, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Dedoussis, GV, Serrano-Rios, M, Morris, AD, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, WHL, Pankow, JS, Sampson, MJ, Kuusisto, J, Laakso, M, Hansen, T, Pedersen, O, Pramstaller, PP, Wichmann, HE, Illig, T, Rudan, I, Wright, AF, Stumvoll, M, Campbell, H, Wilson, JF, Hamsten, A, Bergman, RN, Buchanan, TA, Collins, FS, Mohlke, KL, Tuomilehto, J, Valle, TT, Altshuler, D, Rotter, JI, Siscovick, DS, Penninx, BWJH, Boomsma, DI, Deloukas, P, Spector, TD, Frayling, TM, Ferrucci, L, Kong, A, Thorsteinsdottir, U, Stefansson, K, van Duijn, CM, Aulchenko, YS, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Waterworth, DM, Vollenweider, P, Peltonen, L, Mooser, V, Abecasis, GR, Wareham, NJ, Sladek, R, Froguel, P, Watanabe, RM, Meigs, JB, Groop, L, Boehnke, M, McCarthy, MI, Florez, JC, Consortium, DIAGRAM, Consortium, GIANT, Consortium, GB, Consortium, P, and Investigators, IBMAGIC
Published: 2010

21. Defining the role of common variation in the genomic and biological architecture of adult human height.

Author: Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., Amin, N., Buchkovich, M.L., Croteau-Chonka, D.C., Day, F.R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A.U., Karjalainen, J., Lo, K.S., Locke, A.E., Mägi, R., Mihailov, E., Porcu, E., Randall, J.C., Scherag, A., Vinkhuyzen, A.A., Westra, H.J., Winkler, T.W., Workalemahu, T., Zhao, J.H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G.B., Feenstra, B., Feitosa, M.F., Fischer, K., Fraser, R.M., Goel, A., Justice, A.E., Kanoni, S., Kleber, M.E., Kristiansson, K., Lotay, V., Lui, J.C., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, M.A., Nyholt, D.R., Palmer, C.D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J.S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R.J., Sung, Y.J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S.W., van Setten, J., Van Vliet-Ostaptchouk, J.V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., Zhang, Q., Arveiler, D., Bakker, S.J., Beilby, J., Bergman, R.N., Bergmann, S., Biffar, R., Blangero, J., Boomsma, D.I., Bornstein, S.R., Bovet, P., Brambilla, P., Brown, M.J., Campbell, H., Caulfield, M.J., Chakravarti, A., Collins, R., Collins, F.S., Crawford, D.C., Cupples, L.A., Danesh, J., de Faire, U., den Ruijter, H.M., Erbel, R., Eriksson, J.G., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N.G., Forrester, T., Gansevoort, R.T., Gejman, P.V., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, D.W., Hall, A.S., Harris, T.B., Hattersley, A.T., Heath, A.C., Hicks, A.A., Hindorff, L.A., Hingorani, A.D., Hofman, A., Hovingh, G.K., Humphries, S.E., Hunt, S.C., Hypponen, E., Jacobs, K.B., Jarvelin, M.R., Jousilahti, P., Jula, A.M., Kaprio, J., Kastelein, J.J., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, S.M., Kiemeney, L.A., Kooner, J.S., Koskinen, S., Kovacs, P., Kraja, A.T., Kumari, M., Kuusisto, J., Lakka, T.A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, P.A., Männistö, S., Manunta, P., Marette, A., Matise, T.C., McKnight, B., Meitinger, T., Moll, F.L., Montgomery, G.W., Morris, A.D., Morris, A.P., Murray, J.C., Nelis, M., Ohlsson, C., Oldehinkel, A.J., Ong, K.K., Ouwehand, W.H., Pasterkamp, G., Peters, A., Pramstaller, P.P., Price, J.F., Qi, L., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Rudan, I., Samani, N.J., Saramies, J., Sarzynski, M.A., Schwarz, P.E., Sebert, S., Sever, P., Shuldiner, A.R., Sinisalo, J., Steinthorsdottir, V., Stolk, R.P., Tardif, J.C., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.C., Amouyel, P., Asselbergs, F.W., Assimes, T.L., Bochud, M., Boehm, B.O., Bottinger, E.P., Bouchard, C., Cauchi, S., Chambers, J.C., Chanock, S.J., Cooper, R.S., de Bakker, P.I., Dedoussis, G., Ferrucci, L., Franks, P.W., Froguel, P., Groop, L.C., Haiman, C.A., Hamsten, A., Hayes, M.G., Hui, J., Hunter, D.J., Hveem, K., Jukema, J.W., Kaplan, R.C., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, N.G., März, W., Melbye, M., Moebus, S., Munroe, P.B., Njølstad, I., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Perola, M., Pérusse, L., Powell, J.E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P.M., Rivadeneira, F., Rotter, J.I., Saaristo, T.E., Saleheen, D., Schlessinger, D., Slagboom, P.E., Spector, T.D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., Völzke, H., Walker, M., Wareham, N.J., Watkins, H., Wichmann, H.E., Wilson, J.F., Zanen, P., Heid, I.M., Lindgren, C.M., Mohlke, K.L., Speliotes, E.K., Barroso, I., Fox, C.S., North, K.E., Strachan, D.P., Beckmann, J.S., Berndt, S.I., Boehnke, M., Borecki, I.B., McCarthy, M.I., Metspalu, A., Uitterlinden, A.G., van Duijn, C.M., Willer, C.J., Price, A.L., Lettre, G., Loos, R.J., Weedon, M.N., Ingelsson, E., O'Connell, J.R., Abecasis, G.R., Chasman, D.I., Goddard, M.E., Visscher, P.M., Hirschhorn, J.N., Frayling, T.M., Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., Amin, N., Buchkovich, M.L., Croteau-Chonka, D.C., Day, F.R., Duan, Y., Fall, T., Fehrmann, R., Ferreira, T., Jackson, A.U., Karjalainen, J., Lo, K.S., Locke, A.E., Mägi, R., Mihailov, E., Porcu, E., Randall, J.C., Scherag, A., Vinkhuyzen, A.A., Westra, H.J., Winkler, T.W., Workalemahu, T., Zhao, J.H., Absher, D., Albrecht, E., Anderson, D., Baron, J., Beekman, M., Demirkan, A., Ehret, G.B., Feenstra, B., Feitosa, M.F., Fischer, K., Fraser, R.M., Goel, A., Justice, A.E., Kanoni, S., Kleber, M.E., Kristiansson, K., Lotay, V., Lui, J.C., Mangino, M., Mateo Leach, I., Medina-Gomez, C., Nalls, M.A., Nyholt, D.R., Palmer, C.D., Pasko, D., Pechlivanis, S., Prokopenko, I., Ried, J.S., Ripke, S., Shungin, D., Stancáková, A., Strawbridge, R.J., Sung, Y.J., Tanaka, T., Teumer, A., Trompet, S., van der Laan, S.W., van Setten, J., Van Vliet-Ostaptchouk, J.V., Wang, Z., Yengo, L., Zhang, W., Afzal, U., Arnlöv, J., Arscott, G.M., Bandinelli, S., Barrett, A., Bellis, C., Bennett, A.J., Berne, C., Blüher, M., Bolton, J.L., Böttcher, Y., Boyd, H.A., Buckley, B.M., Caspersen, I.H., Chines, P.S., Clarke, R., Claudi-Boehm, S., Cooper, M., Daw, E.W., De Jong, P.A., Deelen, J., Delgado, G., Denny, J.C., Dhonukshe-Rutten, R., Dimitriou, M., Doney, A.S., Dörr, M., Eklund, N., Eury, E., Folkersen, L., Garcia, M.E., Geller, F., Giedraitis, V., Go, A.S., Grallert, H., Grammer, T.B., Gräßler, J., Grönberg, H., de Groot, L.C., Groves, C.J., Hall, P., Haller, T., Hallmans, G., Hannemann, A., Hartman, C.A., Hassinen, M., Hayward, C., Heard-Costa, N.L., Helmer, Q., Hemani, G., Henders, A.K., Hillege, H.L., Hlatky, M.A., Hoffmann, W., Hoffmann, P., Holmen, O., Houwing-Duistermaat, J.J., Illig, T., Isaacs, A., James, A.L., Johansen, B., Johansson, Å., Jolley, J., Juliusdottir, T., Junttila, J., Kho, A.N., Kinnunen, L., Klopp, N., Kocher, T., Kratzer, W., Lichtner, P., Lind, L., Lindström, J., Lobbens, S., Lorentzon, M., Lu, Y., Lyssenko, V., Magnusson, P.K., Mahajan, A., Maillard, M., McArdle, W.L., McKenzie, C.A., McLachlan, S., McLaren, P.J., Menni, C., Merger, S., Milani, L., Moayyeri, A., Monda, K.L., Morken, M.A., Müller, G., Müller-Nurasyid, M., Musk, A.W., Narisu, N., Nauck, M., Nolte, I.M., Nöthen, M.M., Oozageer, L., Pilz, S., Rayner, N.W., Renstrom, F., Robertson, N.R., Rose, L.M., Roussel, R., Sanna, S., Scharnagl, H., Scholtens, S., Schumacher, F.R., Scott, R.A., Sehmi, J., Seufferlein, T., Shi, J., Silventoinen, K., Smit, J.H., Smith, A.V., Smolonska, J., Stanton, A.V., Stirrups, K., Stott, D.J., Stringham, H.M., Sundström, J., Swertz, M.A., Syvänen, A.C., Tayo, B.O., Tyrer, J.P., van Dijk, S., van Schoor, N.M., van der Velde, N., van Heemst, D., van Oort, F.V., Vermeulen, S.H., Verweij, N., Vonk, J.M., Waite, L.L., Waldenberger, M., Wennauer, R., Wilkens, L.R., Willenborg, C., Wilsgaard, T., Wojczynski, M.K., Wong, A., Wright, A.F., Zhang, Q., Arveiler, D., Bakker, S.J., Beilby, J., Bergman, R.N., Bergmann, S., Biffar, R., Blangero, J., Boomsma, D.I., Bornstein, S.R., Bovet, P., Brambilla, P., Brown, M.J., Campbell, H., Caulfield, M.J., Chakravarti, A., Collins, R., Collins, F.S., Crawford, D.C., Cupples, L.A., Danesh, J., de Faire, U., den Ruijter, H.M., Erbel, R., Eriksson, J.G., Farrall, M., Ferrannini, E., Ferrières, J., Ford, I., Forouhi, N.G., Forrester, T., Gansevoort, R.T., Gejman, P.V., Gieger, C., Golay, A., Gottesman, O., Gudnason, V., Gyllensten, U., Haas, D.W., Hall, A.S., Harris, T.B., Hattersley, A.T., Heath, A.C., Hicks, A.A., Hindorff, L.A., Hingorani, A.D., Hofman, A., Hovingh, G.K., Humphries, S.E., Hunt, S.C., Hypponen, E., Jacobs, K.B., Jarvelin, M.R., Jousilahti, P., Jula, A.M., Kaprio, J., Kastelein, J.J., Kayser, M., Kee, F., Keinanen-Kiukaanniemi, S.M., Kiemeney, L.A., Kooner, J.S., Koskinen, S., Kovacs, P., Kraja, A.T., Kumari, M., Kuusisto, J., Lakka, T.A., Langenberg, C., Le Marchand, L., Lehtimäki, T., Lupoli, S., Madden, P.A., Männistö, S., Manunta, P., Marette, A., Matise, T.C., McKnight, B., Meitinger, T., Moll, F.L., Montgomery, G.W., Morris, A.D., Morris, A.P., Murray, J.C., Nelis, M., Ohlsson, C., Oldehinkel, A.J., Ong, K.K., Ouwehand, W.H., Pasterkamp, G., Peters, A., Pramstaller, P.P., Price, J.F., Qi, L., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Rudan, I., Samani, N.J., Saramies, J., Sarzynski, M.A., Schwarz, P.E., Sebert, S., Sever, P., Shuldiner, A.R., Sinisalo, J., Steinthorsdottir, V., Stolk, R.P., Tardif, J.C., Tönjes, A., Tremblay, A., Tremoli, E., Virtamo, J., Vohl, M.C., Amouyel, P., Asselbergs, F.W., Assimes, T.L., Bochud, M., Boehm, B.O., Bottinger, E.P., Bouchard, C., Cauchi, S., Chambers, J.C., Chanock, S.J., Cooper, R.S., de Bakker, P.I., Dedoussis, G., Ferrucci, L., Franks, P.W., Froguel, P., Groop, L.C., Haiman, C.A., Hamsten, A., Hayes, M.G., Hui, J., Hunter, D.J., Hveem, K., Jukema, J.W., Kaplan, R.C., Kivimaki, M., Kuh, D., Laakso, M., Liu, Y., Martin, N.G., März, W., Melbye, M., Moebus, S., Munroe, P.B., Njølstad, I., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Perola, M., Pérusse, L., Powell, J.E., Power, C., Quertermous, T., Rauramaa, R., Reinmaa, E., Ridker, P.M., Rivadeneira, F., Rotter, J.I., Saaristo, T.E., Saleheen, D., Schlessinger, D., Slagboom, P.E., Spector, T.D., Strauch, K., Stumvoll, M., Tuomilehto, J., Uusitupa, M., Völzke, H., Walker, M., Wareham, N.J., Watkins, H., Wichmann, H.E., Wilson, J.F., Zanen, P., Heid, I.M., Lindgren, C.M., Mohlke, K.L., Speliotes, E.K., Barroso, I., Fox, C.S., North, K.E., Strachan, D.P., Beckmann, J.S., Berndt, S.I., Boehnke, M., Borecki, I.B., McCarthy, M.I., Metspalu, A., Uitterlinden, A.G., van Duijn, C.M., Willer, C.J., Price, A.L., Lettre, G., Loos, R.J., Weedon, M.N., Ingelsson, E., O'Connell, J.R., Abecasis, G.R., Chasman, D.I., Goddard, M.E., Visscher, P.M., Hirschhorn, J.N., and Frayling, T.M.
Abstract: Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
Published: 2014

22. Biological insights from 108 schizophrenia-associated genetic loci

Author: Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Keong, JLC, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Mueller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Borglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Noethen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, O'Donovan, MC, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, K-H, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodriguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Hoffmann, P, Hofman, A, Hollegaard, MV, Hougaard, DM, Ikeda, M, Joa, I, Julia, A, Kahn, RS, Kalaydjieva, L, Karachanak-Yankova, S, Karjalainen, J, Kavanagh, D, Keller, MC, Kennedy, JL, Khrunin, A, Kim, Y, Klovins, J, Knowles, JA, Konte, B, Kucinskas, V, Kucinskiene, ZA, Kuzelova-Ptackova, H, Kahler, AK, Laurent, C, Keong, JLC, Lee, SH, Legge, SE, Lerer, B, Li, M, Li, T, Liang, K-Y, Lieberman, J, Limborska, S, Loughland, CM, Lubinski, J, Lonnqvist, J, Macek, M, Magnusson, PKE, Maher, BS, Maier, W, Mallet, J, Marsal, S, Mattheisen, M, Mattingsdal, M, McCarley, RW, McDonald, C, McIntosh, AM, Meier, S, Meijer, CJ, Melegh, B, Melle, I, Mesholam-Gately, RI, Metspalu, A, Michie, PT, Milani, L, Milanova, V, Mokrab, Y, Morris, DW, Mors, O, Murphy, KC, Murray, RM, Myin-Germeys, I, Mueller-Myhsok, B, Nelis, M, Nenadic, I, Nertney, DA, Nestadt, G, Nicodemus, KK, Nikitina-Zake, L, Nisenbaum, L, Nordin, A, O'Callaghan, E, O'Dushlaine, C, O'Neill, FA, Oh, S-Y, Olincy, A, Olsen, L, Van Os, J, Pantelis, C, Papadimitriou, GN, Papiol, S, Parkhomenko, E, Pato, MT, Paunio, T, Pejovic-Milovancevic, M, Perkins, DO, Pietilainen, O, Pimm, J, Pocklington, AJ, Powell, J, Price, A, Pulver, AE, Purcell, SM, Quested, D, Rasmussen, HB, Reichenberg, A, Reimers, MA, Richards, AL, Roffman, JL, Roussos, P, Ruderfer, DM, Salomaa, V, Sanders, AR, Schall, U, Schubert, CR, Schulze, TG, Schwab, SG, Scolnick, EM, Scott, RJ, Seidman, LJ, Shi, J, Sigurdsson, E, Silagadze, T, Silverman, JM, Sim, K, Slominsky, P, Smoller, JW, So, H-C, Spencer, CCA, Stahl, EA, Stefansson, H, Steinberg, S, Stogmann, E, Straub, RE, Strengman, E, Strohmaier, J, Stroup, TS, Subramaniam, M, Suvisaari, J, Svrakic, DM, Szatkiewicz, JP, Soderman, E, Thirumalai, S, Toncheva, D, Tosato, S, Veijola, J, Waddington, J, Walsh, D, Wang, D, Wang, Q, Webb, BT, Weiser, M, Wildenauer, DB, Williams, NM, Williams, S, Witt, SH, Wolen, AR, Wong, EHM, Wormley, BK, Xi, HS, Zai, CC, Zheng, X, Zimprich, F, Wray, NR, Stefansson, K, Visscher, PM, Adolfsson, R, Andreassen, OA, Blackwood, DHR, Bramon, E, Buxbaum, JD, Borglum, AD, Cichon, S, Darvasi, A, Domenici, E, Ehrenreich, H, Esko, T, Gejman, PV, Gill, M, Gurling, H, Hultman, CM, Iwata, N, Jablensky, AV, Jonsson, EG, Kendler, KS, Kirov, G, Knight, J, Lencz, T, Levinson, DF, Li, QS, Liu, J, Malhotra, AK, McCarroll, SA, McQuillin, A, Moran, JL, Mortensen, PB, Mowry, BJ, Noethen, MM, Ophoff, RA, Owen, MJ, Palotie, A, Pato, CN, Petryshen, TL, Posthuma, D, Rietschel, M, Riley, BP, Rujescu, D, Sham, PC, Sklar, P, St Clair, D, Weinberger, DR, Wendland, JR, Werge, T, Daly, MJ, Sullivan, PF, and O'Donovan, MC
Abstract: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
Published: 2014

23. SnapShot-Seq: A Method for Extracting Genome-Wide, In Vivo mRNA Dynamics from a Single Total RNA Sample

Author: Zuo, Z, Gray, JM, Harmin, DA, Boswell, SA, Cloonan, N, Mullen, TE, Ling, JJ, Miller, N, Kuersten, S, Ma, Y-C, McCarroll, SA, Grimmond, SM, Springer, M, Zuo, Z, Gray, JM, Harmin, DA, Boswell, SA, Cloonan, N, Mullen, TE, Ling, JJ, Miller, N, Kuersten, S, Ma, Y-C, McCarroll, SA, Grimmond, SM, and Springer, M
Abstract: mRNA synthesis, processing, and destruction involve a complex series of molecular steps that are incompletely understood. Because the RNA intermediates in each of these steps have finite lifetimes, extensive mechanistic and dynamical information is encoded in total cellular RNA. Here we report the development of SnapShot-Seq, a set of computational methods that allow the determination of in vivo rates of pre-mRNA synthesis, splicing, intron degradation, and mRNA decay from a single RNA-Seq snapshot of total cellular RNA. SnapShot-Seq can detect in vivo changes in the rates of specific steps of splicing, and it provides genome-wide estimates of pre-mRNA synthesis rates comparable to those obtained via labeling of newly synthesized RNA. We used SnapShot-Seq to investigate the origins of the intrinsic bimodality of metazoan gene expression levels, and our results suggest that this bimodality is partly due to spillover of transcriptional activation from highly expressed genes to their poorly expressed neighbors. SnapShot-Seq dramatically expands the information obtainable from a standard RNA-Seq experiment.
Published: 2014

24. Genome-wide detection and characterization of positive selection in human populations

Author: Sabeti, PC, Varilly, P, Fry, B, Lohmueller, J, Hostetter, E, Cotsapas, C, Xie, X, Byrne, EH, McCarroll, SA, Gaudet, R, Schaffner, SF, Lander, ES, Frazer, KA, Ballinger, DG, Cox, DR, Hinds, DA, Stuve, LL, Gibbs, RA, Belmont, JW, Boudreau, A, Hardenbol, P, Leal, SM, Pasternak, S, Wheeler, DA, Willis, TD, Yu, F, Yang, H, Zeng, C, Gao, Y, Hu, H, Hu, W, Li, C, Lin, W, Liu, S, Pan, H, Tang, X, Wang, J, Wang, W, Yu, J, Zhang, B, Zhang, Q, Zhao, H, Zhou, J, Gabriel, SB, Barry, R, Blumenstiel, B, Camargo, A, Defelice, M, Faggart, M, Goyette, M, Gupta, S, Moore, J, Nguyen, H, Onofrio, RC, Parkin, M, Roy, J, Stahl, E, Winchester, E, Ziaugra, L, Altshuler, D, Shen, Y, Yao, Z, Huang, W, Chu, X, He, Y, Jin, L, Liu, Y, Sun, W, Wang, H, Wang, Y, Xiong, X, Xu, L, Waye, MM, Tsui, SK, Xue, H, Wong, JT, Galver, LM, Fan, JB, Gunderson, K, Murray, SS, Oliphant, AR, Chee, MS, Montpetit, A, Chagnon, F, Ferretti, V, Leboeuf, M, Olivier, JF, Phillips, MS, Roumy, S, Sallée, C, Verner, A, Hudson, TJ, Kwok, PY, Cai, D, Koboldt, DC, Miller, RD, Pawlikowska, L, Taillon-Miller, P, Xiao, M, Tsui, LC, Mak, W, Song, YQ, Tam, PK, Nakamura, Y, Kawaguchi, T, Kitamoto, T, Morizono, T, Nagashima, A, Ohnishi, Y, Sekine, A, Tanaka, T, Tsunoda, T, Deloukas, P, Bird, CP, Delgado, M, Dermitzakis, ET, Gwilliam, R, Hunt, S, Morrison, J, Powell, D, Stranger, BE, Whittaker, P, Bentley, DR, Daly, MJ, de Bakker, PI, Barrett, J, Chretien, YR, Maller, J, McCarroll, S, Patterson, N, Pe'er, I, Price, A, Purcell, S, Richter, DJ, Sabeti, P, Saxena, R, Sham, PC, Stein, LD, Krishnan, L, Smith, AV, Tello-Ruiz, MK, Thorisson, GA, Chakravarti, A, Chen, PE, Cutler, DJ, Kashuk, CS, Lin, S, Abecasis, GR, Guan, W, Li, Y, Munro, HM, Qin, ZS, Thomas, DJ, McVean, G, Auton, A, Bottolo, L, Cardin, N, Eyheramendy, S, Freeman, C, Marchini, J, Myers, S, Spencer, C, Stephens, M, Donnelly, P, Cardon, LR, Clarke, G, Evans, DM, Morris, AP, Weir, BS, Johnson, TA, Mullikin, JC, Sherry, ST, Feolo, M, Skol, A, Zhang, H, Matsuda, I, Fukushima, Y, Macer, DR, Suda, E, Rotimi, CN, Adebamowo, CA, Ajayi, I, Aniagwu, T, Marshall, PA, Nkwodimmah, C, Royal, CD, Leppert, MF, Dixon, M, Peiffer, A, Qiu, R, Kent, A, Kato, K, Niikawa, N, Adewole, IF, Knoppers, BM, Foster, MW, Clayton, EW, Watkin, J, Muzny, D, Nazareth, L, Sodergren, E, Weinstock, GM, Yakub, I, Birren, BW, Wilson, RK, Fulton, LL, Rogers, J, Burton, J, Carter, NP, Clee, CM, Griffiths, M, Jones, MC, McLay, K, Plumb, RW, Ross, MT, Sims, SK, Willey, DL, Chen, Z, Han, H, Kang, L, Godbout, M, Wallenburg, JC, L'Archevêque, P, Bellemare, G, Saeki, K, An, D, Fu, H, Li, Q, Wang, Z, Wang, R, Holden, AL, Brooks, LD, McEwen, JE, Guyer, MS, Wang, VO, Peterson, JL, Shi, M, Spiegel, J, Sung, LM, Zacharia, LF, Collins, FS, Kennedy, K, Jamieson, R, and Stewart, J
Subjects: Models, Molecular, Population, Single-nucleotide polymorphism, Human genetic variation, Biology, Polymorphism, Single Nucleotide, Article, Antiporters, Gene Frequency, Humans, International HapMap Project, Selection, Genetic, education, Selection (genetic algorithm), Genetics, education.field_of_study, Multidisciplinary, Natural selection, Geography, Edar Receptor, Genome, Human, Haplotype, Regional Index: Eurasia, Protein Structure, Tertiary, Europe, Genetics, Population, Haplotypes, Human genome
Abstract: With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia. ©2007 Nature Publishing Group., link_to_OA_fulltext
Published: 2007

25. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

Author: GIANT Consortium, MAGIC Consortium, GLGC Consortium, Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, AU., Wheeler, E., Glazer, NL., Bouatia-Naji, N., Gloyn, AL., Lindgren, CM., Mägi, R., Morris, AP., Randall, J., Johnson, T., Elliott, P., Rybin, D., Thorleifsson, G., Steinthorsdottir, V., Henneman, P., Grallert, H., Dehghan, A., Hottenga, JJ., Franklin, CS., Navarro, P., Song, K., Goel, A., Perry, JR., Egan, JM., Lajunen, T., Grarup, N., Sparsø, T., Doney, A., Voight, BF., Stringham, HM., Li, M., Kanoni, S., Shrader, P., Cavalcanti-Proença, C., Kumari, M., Qi, L., Timpson, NJ., Gieger, C., Zabena, C., Rocheleau, G., Ingelsson, E., An, P., O'Connell, J., Luan£££Jian'an£££ J., Elliott, A., McCarroll, SA., Payne, F., Roccasecca, RM., Pattou, F., Sethupathy, P., Ardlie, K., Ariyurek, Y., Balkau, B., Barter, P., Beilby, JP., Ben-Shlomo, Y., Benediktsson, R., Bennett, AJ., Bergmann, S., Bochud, M., Boerwinkle, E., Bonnefond, A., Bonnycastle, LL., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, SJ., Charpentier, G., Chen, YD., Chines, P., Clarke, R., Coin, LJ., Cooper, MN., Cornelis, M., Crawford, G., Crisponi, L., Day, IN., de Geus EJ., Delplanque, J., Dina, C., Erdos, MR., Fedson, AC., Fischer-Rosinsky, A., Forouhi, NG., Fox, CS., Frants, R., Franzosi, MG., Galan, P., Goodarzi, MO., Graessler, J., Groves, CJ., Grundy, S., Gwilliam, R., Gyllensten, U., Hadjadj, S., Hallmans, G., Hammond, N., Han, X., Hartikainen, AL., Hassanali, N., Hayward, C., Heath, SC., Hercberg, S., Herder, C., Hicks, AA., Hillman, DR., Hingorani, AD., Hofman, A., Hui, J., Hung, J., Isomaa, B., Johnson, PR., Jørgensen, T., Jula, A., Kaakinen, M., Kaprio, J., Kesaniemi, YA., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, KO., Lathrop, GM., Lawlor, DA., Le Bacquer, O., Lecoeur, C., Li, Y., Lyssenko, V., Mahley, R., Mangino, M., Manning, AK., Martínez-Larrad£££María Teresa£££ MT., McAteer, JB., McCulloch, LJ., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, BD., Morken, MA., Mukherjee, S., Naitza, S., Narisu, N., Neville, MJ., Oostra, BA., Orrù, M., Pakyz, R., Palmer, CN., Paolisso, G., Pattaro, C., Pearson, D., Peden, JF., Pedersen, NL., Perola, M., Pfeiffer, AF., Pichler, I., Polasek, O., Posthuma, D., Potter, SC., Pouta, A., Province, MA., Psaty, BM., Rathmann, W., Rayner, NW., Rice, K., Ripatti, S., Rivadeneira, F., Roden, M., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, AA., Scheet, P., Scott, LJ., Seedorf, U., Sharp, SJ., Shields, B., Sigurðsson, G., Sijbrands, EJ., Silveira, A., Simpson, L., Singleton, A., Smith, NL., Sovio, U., Swift, A., Syddall, H., Syvänen, AC., Tanaka, T., Thorand, B., Tichet, J., Tönjes, A., Tuomi, T., Uitterlinden, AG., van Dijk KW., van Hoek, M., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, PJ., Walley, A., Walters, GB., Ward, KL., Watkins, H., Weedon, MN., Wild, SH., Willemsen, G., Witteman, JC., Yarnell, JW., Zeggini, E., Zelenika, D., Zethelius, B., Zhai, G., Zhao, JH., Zillikens, MC., Borecki, IB., Loos, RJ., Meneton, P., Magnusson, PK., Nathan, DM., Williams, GH., Hattersley, AT., Silander, K., Salomaa, V., Smith, GD., Bornstein, SR., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, AR., Cooper, C., Dedoussis, GV., Serrano-Ríos, M., Morris, AD., Lind, L., Palmer, LJ., Hu, FB., Franks, PW., Ebrahim, S., Marmot, M., Kao, WH., Pankow, JS., Sampson, MJ., Kuusisto, J., Laakso, M., Hansen, T., Pedersen, O., Pramstaller, PP., Wichmann, HE., Illig, T., Rudan, I., Wright, AF., Stumvoll, M., Campbell, H., Wilson, JF., Hamsten, A., Bergman, RN., Buchanan, TA., Collins, FS., Mohlke, KL., Tuomilehto, J., Valle, TT., Altshuler, D., Rotter, JI., Siscovick, DS., Penninx, BW., Boomsma, ID., Deloukas, P., Spector, TD., Frayling, TM., Ferrucci, L., Kong, A., Thorsteinsdottir, U., Stefansson, K., van Duijn CM., Aulchenko, YS., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, MR., Waterworth, DM., Vollenweider, P., Peltonen, L., Mooser, V., Abecasis, RG., Wareham, NJ., Sladek, R., Froguel, P., Watanabe, RM., Meigs, JB., Groop, L., Boehnke, M., McCarthy, MI., Florez, JC., Barroso£££Inês£££ I., Fox, C.S., Liu, Y., White, C.C., Feitosa, M., Smith, A.V., Heard-Costa, N., Lohman, K., Johnson, A.D., Foster, M.C., Greenawalt, D.M., Griffin, P., Ding, J., Newman, A.B., Tylavsky, F., Miljkovic, I., Kritchevsky, S.B., Launer, L., Garcia, M., Eiriksdottir, G., Carr, J.J., Gudnason, V., Harris, T.B., Cupples, L.A., Borecki, I.B., GIANT Consortium, MAGIC Consortium, GLGC Consortium, Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, AU., Wheeler, E., Glazer, NL., Bouatia-Naji, N., Gloyn, AL., Lindgren, CM., Mägi, R., Morris, AP., Randall, J., Johnson, T., Elliott, P., Rybin, D., Thorleifsson, G., Steinthorsdottir, V., Henneman, P., Grallert, H., Dehghan, A., Hottenga, JJ., Franklin, CS., Navarro, P., Song, K., Goel, A., Perry, JR., Egan, JM., Lajunen, T., Grarup, N., Sparsø, T., Doney, A., Voight, BF., Stringham, HM., Li, M., Kanoni, S., Shrader, P., Cavalcanti-Proença, C., Kumari, M., Qi, L., Timpson, NJ., Gieger, C., Zabena, C., Rocheleau, G., Ingelsson, E., An, P., O'Connell, J., Luan£££Jian'an£££ J., Elliott, A., McCarroll, SA., Payne, F., Roccasecca, RM., Pattou, F., Sethupathy, P., Ardlie, K., Ariyurek, Y., Balkau, B., Barter, P., Beilby, JP., Ben-Shlomo, Y., Benediktsson, R., Bennett, AJ., Bergmann, S., Bochud, M., Boerwinkle, E., Bonnefond, A., Bonnycastle, LL., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, SJ., Charpentier, G., Chen, YD., Chines, P., Clarke, R., Coin, LJ., Cooper, MN., Cornelis, M., Crawford, G., Crisponi, L., Day, IN., de Geus EJ., Delplanque, J., Dina, C., Erdos, MR., Fedson, AC., Fischer-Rosinsky, A., Forouhi, NG., Fox, CS., Frants, R., Franzosi, MG., Galan, P., Goodarzi, MO., Graessler, J., Groves, CJ., Grundy, S., Gwilliam, R., Gyllensten, U., Hadjadj, S., Hallmans, G., Hammond, N., Han, X., Hartikainen, AL., Hassanali, N., Hayward, C., Heath, SC., Hercberg, S., Herder, C., Hicks, AA., Hillman, DR., Hingorani, AD., Hofman, A., Hui, J., Hung, J., Isomaa, B., Johnson, PR., Jørgensen, T., Jula, A., Kaakinen, M., Kaprio, J., Kesaniemi, YA., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, KO., Lathrop, GM., Lawlor, DA., Le Bacquer, O., Lecoeur, C., Li, Y., Lyssenko, V., Mahley, R., Mangino, M., Manning, AK., Martínez-Larrad£££María Teresa£££ MT., McAteer, JB., McCulloch, LJ., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, BD., Morken, MA., Mukherjee, S., Naitza, S., Narisu, N., Neville, MJ., Oostra, BA., Orrù, M., Pakyz, R., Palmer, CN., Paolisso, G., Pattaro, C., Pearson, D., Peden, JF., Pedersen, NL., Perola, M., Pfeiffer, AF., Pichler, I., Polasek, O., Posthuma, D., Potter, SC., Pouta, A., Province, MA., Psaty, BM., Rathmann, W., Rayner, NW., Rice, K., Ripatti, S., Rivadeneira, F., Roden, M., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, AA., Scheet, P., Scott, LJ., Seedorf, U., Sharp, SJ., Shields, B., Sigurðsson, G., Sijbrands, EJ., Silveira, A., Simpson, L., Singleton, A., Smith, NL., Sovio, U., Swift, A., Syddall, H., Syvänen, AC., Tanaka, T., Thorand, B., Tichet, J., Tönjes, A., Tuomi, T., Uitterlinden, AG., van Dijk KW., van Hoek, M., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, PJ., Walley, A., Walters, GB., Ward, KL., Watkins, H., Weedon, MN., Wild, SH., Willemsen, G., Witteman, JC., Yarnell, JW., Zeggini, E., Zelenika, D., Zethelius, B., Zhai, G., Zhao, JH., Zillikens, MC., Borecki, IB., Loos, RJ., Meneton, P., Magnusson, PK., Nathan, DM., Williams, GH., Hattersley, AT., Silander, K., Salomaa, V., Smith, GD., Bornstein, SR., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, AR., Cooper, C., Dedoussis, GV., Serrano-Ríos, M., Morris, AD., Lind, L., Palmer, LJ., Hu, FB., Franks, PW., Ebrahim, S., Marmot, M., Kao, WH., Pankow, JS., Sampson, MJ., Kuusisto, J., Laakso, M., Hansen, T., Pedersen, O., Pramstaller, PP., Wichmann, HE., Illig, T., Rudan, I., Wright, AF., Stumvoll, M., Campbell, H., Wilson, JF., Hamsten, A., Bergman, RN., Buchanan, TA., Collins, FS., Mohlke, KL., Tuomilehto, J., Valle, TT., Altshuler, D., Rotter, JI., Siscovick, DS., Penninx, BW., Boomsma, ID., Deloukas, P., Spector, TD., Frayling, TM., Ferrucci, L., Kong, A., Thorsteinsdottir, U., Stefansson, K., van Duijn CM., Aulchenko, YS., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, MR., Waterworth, DM., Vollenweider, P., Peltonen, L., Mooser, V., Abecasis, RG., Wareham, NJ., Sladek, R., Froguel, P., Watanabe, RM., Meigs, JB., Groop, L., Boehnke, M., McCarthy, MI., Florez, JC., Barroso£££Inês£££ I., Fox, C.S., Liu, Y., White, C.C., Feitosa, M., Smith, A.V., Heard-Costa, N., Lohman, K., Johnson, A.D., Foster, M.C., Greenawalt, D.M., Griffin, P., Ding, J., Newman, A.B., Tylavsky, F., Miljkovic, I., Kritchevsky, S.B., Launer, L., Garcia, M., Eiriksdottir, G., Carr, J.J., Gudnason, V., Harris, T.B., Cupples, L.A., and Borecki, I.B.
Abstract: Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in
Published: 2012

26. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author: Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, Loos, RJF, Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, and Loos, RJF
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
Published: 2010

27. Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function.

Author: Allison, DB, Raychaudhuri, S, Korn, JM, McCarroll, SA, International Schizophrenia Consortium, Altshuler, D, Sklar, P, Purcell, S, Daly, MJ, Allison, DB, Raychaudhuri, S, Korn, JM, McCarroll, SA, International Schizophrenia Consortium, Altshuler, D, Sklar, P, Purcell, S, and Daly, MJ
Abstract: Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied "pathway" analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package.
Published: 2010

28. Erratum: Corrigendum: Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Author: Voight, BF, Scott, LJ, Steinthorsdottir, V, Morris, AP, Dina, C, Welch, RP, Zeggini, E, Huth, C, Aulchenko, YS, Thorleifsson, G, McCulloch, LJ, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, CJ, Raychaudhuri, S, McCarroll, SA, Langenberg, C, Hofmann, OM, Dupuis, J, Qi, L, Segrè, AV, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, AJ, Blagieva, R, Boerwinkle, E, Bonnycastle, LL, Boström, KB, Bravenboer, B, Bumpstead, S, Burtt, NP, Charpentier, G, Chines, PS, Cornelis, M, Couper, DJ, Crawford, G, Doney, AS, Elliott, KS, Elliott, AL, Erdos, MR, Fox, CS, Franklin, CS, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, CJ, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, AU, Johnson, PR, Jørgensen, T, Kao, WH, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, CM, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, MA, Narisu, N, Nilsson, P, Owen, KR, Payne, F, Perry, JR, Petersen, AK, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, NW, Robertson, NR, Rocheleau, G, Roden, M, Sampson, MJ, Saxena, R, Shields, BM, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, HM, Sun, Q, Swift, AJ, Thorand, B, Tichet, J, Tuomi, T, van Dam, RM, van Haeften, TW, van Herpt, T, van Vliet-Ostaptchouk, JV, Walters, GB, Weedon, MN, Wijmenga, C, Witteman, J, Bergman, RN, Cauchi, S, Collins, FS, Gloyn, AL, Gyllensten, U, Hansen, T, Hide, WA, Hitman, GA, Hofman, A, Hunter, DJ, Hveem, K, Laakso, M, Mohlke, KL, Morris, AD, Palmer, CN, Pramstaller, PP, Rudan, I, Sijbrands, E, Stein, LD, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, NJ, Watanabe, RM, Abecasis, GR, Boehm, BO, Campbell, H, Daly, MJ, Hattersley, AT, Hu, FB, Meigs, JB, Pankow, JS, Pedersen, O, Wichmann, HE, Barroso, I, Florez, JC, Frayling, TM, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, JF, Illig, T, Froguel, P, van Duijn, CM, Stefansson, K, Altshuler, D, Boehnke, M, and McCarthy, MI
Subjects: Genetics, Scale (ratio), medicine, Susceptibility locus, Type 2 diabetes, Biology, medicine.disease, Genetic association
Published: 2011

29. Copy number variation in bipolar disorder

Author: Green, EK, Rees, E, Walters, JTR, Smith, K-G, Forty, L, Grozeva, D, Moran, JL, Sklar, P, Ripke, S, Chambert, KD, Genovese, G, McCarroll, SA, Jones, I, Jones, L, Owen, MJ, O’Donovan, MC, Craddock, N, and Kirov, G
Abstract: Large (>100 kb), rare (<1% in the population) copy number variants (CNVs) have been shown to confer risk for schizophrenia (SZ), but the findings for bipolar disorder (BD) are less clear. In a new BD sample from the United Kingdom (n = 2591), we have examined the occurrence of CNVs and compared this with previously reported samples of 6882 SZ and 8842 control subjects. When combined with previous data, we find evidence for a contribution to BD for three SZ-associated CNV loci: duplications at 1q21.1 (P = 0.022), deletions at 3q29 (P = 0.03) and duplications at 16p11.2 (P = 2.3 × 10−4). The latter survives multiple-testing correction for the number of recurrent large CNV loci in the genome. Genes in 20 regions (total of 55 genes) were enriched for rare exonic CNVs among BD cases, but none of these survives correction for multiple testing. Finally, our data provide strong support for the hypothesis of a lesser contribution of very large (>500 kb) CNVs in BD compared with SZ, most notably for deletions >1 Mb (P = 9 × 10−4).
Published: 2016
Full Text: View/download PDF

30. Defining the role of common variation in the genomic and biological architecture of adult human height

Author: Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, Van Der Laan, S, Van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, De Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, Van Der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Speliotes, E, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Boehnke, M, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, Van Duijn, C, Franke, L, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Hirschhorn, J, Frayling, T, Medical Research Council (MRC), APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Psychiatry, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Wood, Ar, Pers, Th, Chu, Ay, Buchkovich, Ml, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Locke, Ae, Randall, Jc, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Zhao, Jh, Ehret, Gb, Feitosa, Mf, Fraser, Rm, Justice, Ae, Kleber, Me, Lui, Jc, MATEO LEACH, I, MEDINA GOMEZ, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Strawbridge, Rj, Sung, Yj, VAN DER LAAN, Sw, VAN SETTEN, J, VAN VLIET OSTAPTCHOUK, Jv, Arnlöv, J, Arscott, Gm, Bennett, Aj, Bolton, Jl, Boyd, Ha, Buckley, Bm, Caspersen, Ih, CLAUDI BOEHM, S, Daw, Ew, DE JONG, Pa, Denny, Jc, DHONUKSHE RUTTEN, R, Garcia, Me, Grammer, Tb, DE GROOT, Lc, Groves, Cj, Hartman, Ca, HEARD COSTA, Nl, Henders, Ak, Hillege, Hl, Hlatky, Ma, HOUWING DUISTERMAAT, Jj, James, Al, Johansson, A, Kho, An, Magnusson, Pk, Mcardle, Wl, Mckenzie, Ca, Mclaren, Pj, Monda, Kl, Morken, Ma, MÜLLER NURASYID, M, Musk, Aw, Nolte, Im, Nöthen, Mm, Rayner, Nw, Robertson, Nr, Rose, Lm, Schumacher, Fr, Scott, Ra, Smit, Jh, Smith, Av, Stanton, Av, Stott, Dj, Stringham, Hm, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Tyrer, Jp, VAN DIJK, S, VAN SCHOOR, Nm, VAN DER VELDE, N, VAN HEEMST, D, VAN OORT, Fv, Vermeulen, Sh, Vonk, Jm, Waite, Ll, Wilkens, Lr, Wojczynski, Mk, Wright, Af, Bakker, Sj, Bergman, Rn, Boomsma, Di, Bornstein, Sr, Brown, Mj, Caulfield, Mj, Crawford, Dc, Cupples, La, DE FAIRE, U, DEN RUIJTER, Hm, Eriksson, Jg, Forouhi, Ng, Gansevoort, Rt, Gejman, Pv, Haas, Dw, Harris, Tb, Hattersley, At, Heath, Ac, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hovingh, Gk, Humphries, Se, Hunt, Sc, Jacobs, Kb, Jarvelin, Mr, Jula, Am, Kastelein, Jj, KEINANEN KIUKAANNIEMI, Sm, Kiemeney, La, Kraja, At, Lakka, Ta, LE MARCHAND, L, Madden, Pa, Manunta, Paolo, Matise, Tc, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pramstaller, Pp, Price, Jf, Raitakari, Ot, Rao, Dc, Rice, Tk, Samani, Nj, Sarzynski, Ma, Schwarz, Pe, Shuldiner, Ar, Stolk, Rp, Tardif, Jc, Vohl, Mc, ELECTRONIC MEDICAL RECORDS AND GENOMICS, Consortium, Migen, Consortium, Page, Consortium, LIFELINES COHORT, Study, Asselbergs, Fw, Assimes, Tl, Boehm, Bo, Bottinger, Ep, Chambers, Jc, Chanock, Sj, DE BAKKER, Pi, Franks, Pw, Groop, Lc, Haiman, Ca, Hayes, Mg, Hunter, Dj, Jukema, Jw, Kaplan, Rc, Martin, Ng, Munroe, Pb, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Powell, Je, Ridker, Pm, Rotter, Ji, Saaristo, Te, Slagboom, Pe, Spector, Td, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, North, Ke, Strachan, Dp, Berndt, Si, Borecki, Ib, Mccarthy, Mi, Uitterlinden, Ag, VAN DUIJN, Cm, Willer, Cj, Price, Al, Loos, Rj, Weedon, Mn, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, Tm, Epidemiology, Surgery, Public Health, Internal Medicine, Erasmus MC other, Genetic Identification, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Biological Psychology, AIMMS, Functional Genomics, EMGO+ - Lifestyle, Overweight and Diabetes, Wood, AR, Vadantam, S, Hypponen, Elina, Frayling, TM, Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Amin N., Buchkovich M.L., Croteau-Chonka D.C., Day F.R., Duan Y., Fall T., Fehrmann R., Ferreira T., Jackson A.U., Karjalainen J., Lo K.S., Locke A.E., Magi R., Mihailov E., Porcu E., Randall J.C., Scherag A., Vinkhuyzen A.A.E., Westra H.-J., Winkler T.W., Workalemahu T., Zhao J.H., Absher D., Albrecht E., Anderson D., Baron J., Beekman M., Demirkan A., Ehret G.B., Feenstra B., Feitosa M.F., Fischer K., Fraser R.M., Goel A., Gong J., Justice A.E., Kanoni S., Kleber M.E., Kristiansson K., Lim U., Lotay V., Lui J.C., Mangino M., Leach I.M., Medina-Gomez C., Nalls M.A., Nyholt D.R., Palmer C.D., Pasko D., Pechlivanis S., Prokopenko I., Ried J.S., Ripke S., Shungin D., Stancakova A., Strawbridge R.J., Sung Y.J., Tanaka T., Teumer A., Trompet S., Van Der Laan S.W., Van Setten J., Van Vliet-Ostaptchouk J.V., Wang Z., Yengo L., Zhang W., Afzal U., Arnlov J., Arscott G.M., Bandinelli S., Barrett A., Bellis C., Bennett A.J., Berne C., Bluher M., Bolton J.L., Bottcher Y., Boyd H.A., Bruinenberg M., Buckley B.M., Buyske S., Caspersen I.H., Chines P.S., Clarke R., Claudi-Boehm S., Cooper M., Daw E.W., De Jong P.A., Deelen J., Delgado G., Denny J.C., Dhonukshe-Rutten R., Dimitriou M., Doney A.S.F., Dorr M., Eklund N., Eury E., Folkersen L., Garcia M.E., Geller F., Giedraitis V., Go A.S., Grallert H., Grammer T.B., Grassler J., Gronberg H., De Groot L.C.P.G.M., Groves C.J., Haessler J., Hall P., Haller T., Hallmans G., Hannemann A., Hartman C.A., Hassinen M., Hayward C., Heard-Costa N.L., Helmer Q., Hemani G., Henders A.K., Hillege H.L., Hlatky M.A., Hoffmann W., Hoffmann P., Holmen O., Houwing-Duistermaat J.J., Illig T., Isaacs A., James A.L., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., Mahajan A., Maillard M., McArdle W.L., McKenzie C.A., McLachlan S., McLaren P.J., Menni C., Merger S., Milani L., Moayyeri A., Monda K.L., Morken M.A., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen M.M., Oozageer L., Pilz S., Rayner N.W., Renstrom F., Robertson N.R., Rose L.M., Roussel R., Sanna S., Scharnagl H., Scholtens S., Schumacher F.R., Schunkert H., Scott R.A., Sehmi J., Seufferlein T., Shi J., Silventoinen K., Smit J.H., Smith A.V., Smolonska J., Stanton A.V., Stirrups K., Stott D.J., Stringham H.M., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., Powell J.E., Power C., Quertermous T., Rauramaa R., Reinmaa E., Ridker P.M., Rivadeneira F., Rotter J.I., Saaristo T.E., Saleheen D., Schlessinger D., Slagboom P.E., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., Barroso I., Fox C.S., North K.E., Strachan D.P., Beckmann J.S., Berndt S.I., Boehnke M., Borecki I.B., McCarthy M.I., Metspalu A., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.
Subjects: Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, Medizin, Genome-wide association study, Adult, Analysis of Variance, Body Height/genetics, European Continental Ancestry Group/genetics, Genetic Variation/genetics, Genetics, Population, Genome-Wide Association Study/methods, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide/genetics, heritability, 0302 clinical medicine, Genome-wide, SNPS, snps, Genetics & Heredity, ddc:616, Genetics, Medical And Health Sciences, 0303 health sciences, education.field_of_study, variants, GENETIC-VARIATION, Biological Sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], body height, genetic-variation, Life Sciences & Biomedicine, Single Nucleotide/genetics, Human, European Continental Ancestry Group, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, NO, complex traits, 03 medical and health sciences, Genetic variation, heritability, adult, height, Polymorphism, Human height, PAGEGE Consortium, education, Gene, VLAG, 030304 developmental biology, Global Nutrition, Wereldvoeding, genome-wide association study, Science & Technology, Whites, Oligonucleotide Array Sequence Analysi, MUTATIONS, COMPLEX TRAITS, ta1184, Klinisk medicin, population genetics, Genetic Variation, Heritability, ta3121, mutations, Genetic architecture, Body Height, genetic variation, MIGen Consortium, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Clinical Medicine, 030217 neurology & neurosurgery, height, LifeLines Cohort Study, Developmental Biology, Genome-Wide Association Study
Abstract: Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
Published: 2014

31. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Author: Anita Thapar, Lena Backlund, Lindsey Kent, Walter J. Muir, A. Jeremy Willsey, Sandra K. Loo, Michael Boehnke, Christa Lese Martin, Ania Korszun, Guiomar Oliveira, Veronica J. Vieland, Stephen W. Scherer, René S. Kahn, Darina Czamara, Jeremy R. Parr, Michael E. Goddard, Willem A. Nolen, Josep Antoni Ramos-Quiroga, Stephen Sanders, Karola Rehnstroem, Nelson B. Freimer, Erin N. Smith, Ann Olincy, Ingrid Melle, Myrna M. Weissman, James A. Knowles, William Byerley, Aravinda Chakravarti, Shaun Purcell, Jens Treutlein, Sebastian Zoellner, Hakon Hakonarson, Susanne Lucae, Markus M. Noethen, Ian B. Hickie, Marion Friedl, Srinivasa Thirumalai, Stephen Newhouse, Joseph Piven, Andrew M. McIntosh, Cathryn M. Lewis, Srdjan Djurovic, Francis J. McMahon, Ayman H. Fanous, Bernie Devlin, Steven A. McCarroll, Alan F. Schatzberg, Peter Szatmari, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Gerard van Grootheest, Phil Lee, Richard Anney, Elaine K. Green, Geraldine Dawson, Joseph A. Sergeant, Digby Quested, Magdalena Gross, Jack D. Barchas, Nicholas G. Martin, Timothy W. Yu, Jouke-Jan Hottenga, Mark Lathrop, Federica Tozzi, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Sandra Meier, Louise Gailagher, David A. Collier, Farooq Amin, Michael C. Neale, Martin Schalling, Lieuwe de Haan, Bru Cormand, Falk W. Lohoff, Jennifer Crosbie, Howard J. Edenberg, Aarno Palotie, Johannes H. Smit, Robert Freedman, Katherine Gordon-Smith, Michele L. Pergadia, Enda M. Byrne, Hans-Christoph Steinhausen, Benjamin M. Neale, Anjali K. Henders, Michele T. Pato, Manuel Mattheisen, Urban Ösby, Edward M. Scolnick, Evaristus A. Nwulia, Fritz Poustka, Gonneke Willemsen, Andrew C. Heath, David St. Cair, Emma M. Quinn, I. Nicol Ferrier, John R. Kelsoe, Vanessa Hus, Andrew McQuillin, John P. Rice, William M. McMahon, Joseph Biederman, Danyu Lin, Wolfgang Maier, Frans G. Zitman, Josephine Elia, Nicholas J. Schork, Stéphane Jamain, Lizzy Rossin, Jubao Duan, Ingrid Agartz, Devin Absher, Jordan W. Smoller, Matthew W. State, Richard M. Myers, Shrikant Mane, Carlos N. Pato, William E. Bunney, Marian L. Hamshere, Manfred Uhr, Nicholas John Craddock, Astrid M. Vicente, Tobias Banaschewski, David Curtis, Anne Farmer, Scott D. Gordon, Anna K. Kaehler, Eric M. Morrow, Marcella Rietschel, Patrik K. E. Magnusson, Klaus-Peter Lesch, Rebecca McKinney, Jana Strohmaier, Thomas F. Wienker, Pablo V. Gejman, Douglas Blackwood, Maria Helena Pinto de Azevedo, Tiffany A. Greenwood, Don H. Linszen, Daniel L. Koller, Richard Bruggeman, Vinay Puri, Naomi R. Wray, Stanley J. Watson, Elena Maestrini, Valentina Moskvina, Frank Dudbridge, Danielle Posthuma, Edward G. Jones, Lambertus Klei, Sarah E. Bergen, Fan Meng, Steven P. Hamilton, Guy A. Rouleau, Pierandrea Muglia, Mikael Landén, Stephanie H. Witt, Laramie E. Duncan, Stanley Zammit, Judith A. Badner, Florian Holsboer, Eco J. C. de Geus, Daniel Moreno-De-Luca, Benjamin S. Pickard, Gunnar Morken, Michael Conlon O'Donovan, Michael Steffens, Kathryn Roeder, Dorret I. Boomsma, Paul D. Shilling, Stephan Ripke, Nigel Williams, Jeremy M. Silverman, David Craig, Mark J. Daly, Michael Bauer, Detelina Grozeva, Markus J. Schwarz, Peter Holmans, Hugh Gurling, T. Scott Stroup, Aribert Rothenberger, Gary Donohoe, Eric Fombonne, Joseph D. Buxbaum, Matthew Flicldnger, Bryan J. Mowry, Thomas Hansen, Ina Giegling, Grant W. Montgomery, Caroline M. Nievergelt, Susan L. Smalley, Jung-Ying Tzeng, David H. Ledbetter, Christopher A. Walsh, Gerard D. Schellenberg, Sarah E. Medland, Robert D. Oades, James B. Potash, Dan E. Arking, Johannes Schumacher, Michael Gill, James J. McGough, Jennifer L. Moran, Donald W. Black, Sian Caesar, Neelroop N. Parikshak, Ian W. Craig, Sabine M. Klauck, Wade H. Berrettini, T. Foroud, Peter P. Zandi, Inez Myin-Germeys, Marcus Ising, Sven Cichon, Alexandre A. Todorov, Mònica Bayés, Thomas Werge, Susan L. Slager, Stanley I. Shyn, Jim van Os, Derek W. Morris, Douglas M. Ruderfer, Thomas W. Muehleisen, Matthew C. Keller, Susmita Datta, Ian Jones, John B. Vincent, James L. Kennedy, Anthony P. Monaco, Jianxin Shi, Dale R. Nyholt, Bruno Etain, Christine Fraser, Paul Cormican, Miguel Casas, Radhika Kandaswamy, Gerome Breen, Stephen V. Faraone, Jonna Kuntsi, Thomas Bettecken, Witte J.G. Hoogendijk, Nancy G. Buccola, Franziska Degenhardt, Lyudmila Georgieva, Marion Leboyer, Alan R. Sanders, John Strauss, Dan Rujescu, Russell Schachar, Helena Medeiros, Lisa Jones, Peter M. Visscher, Lauren A. Weiss, René Breuer, John I. Nurnberger, Andreas Reif, Phoenix Kwan, Vihra Milanova, Chunyu Liu, Martin A. Kohli, Donald J. MacIntyre, Nicholas Bass, Khalid Choudhury, Edwin H. Cook, Catherine Lord, Andrew D. Paterson, Jobst Meyer, Richard P. Ebstein, Zhaoming Zhao, Niklas Laengstroem, Thomas G. Schulze, Peter Propping, Wei Xu, Robert C. Thompson, Kimberly Chambert, Jonathan Pimm, Ivan Nikolov, Pamela A. F. Madden, Kevin A. McGhee, Jacob Lawrence, Jan K. Buitelaar, Andres Ingason, Christine M. Freitag, Robert Krasucki, Wiepke Cahn, Rita M. Cantor, Christina M. Hultman, Melvin G. McInnis, Catalina Betancur, Eftichia Duketis, Michael T. Murtha, Thomas H. Wassink, Philip Asherson, John S. Witte, Elaine Kenny, Edmund J.S. Sonuga-Barke, Lydia Krabbendam, Line Olsen, Agatino Battaglia, Laura J. Scott, Annette M. Hartmann, Yunjung Kim, Richard O. Day, Edwin J. C. G. van den Oord, Ole A. Andreassen, Herbert Roeyers, Michael John Owen, Colm O'Dushlaine, Peng Zhang, Morten Mattingsdal, Michael L. Cuccaro, Margaret A. Pericak-Vance, Joachim Hallmayer, Jun Li, Pamela B. Mahon, Elisabeth B. Binder, William A. Scheftner, Daniel H. Geschwind, Christel M. Middeldorp, Josef Frank, Keith Matthews, Jennifer K. Lowe, Paul Lichtenstein, Verneri Anttila, Pamela Sklar, Szabocls Szelinger, Roel A. Ophoff, Peter McGuffin, Stefan Herms, Bettina Konte, George Kirov, Hilary Coon, Maria Hipolito, Louise Frisén, Kenneth S. Kendler, Frank Bellivier, James S. Sutdiffe, Jeffrey A. Lieberman, Todd Lencz, Susanne Hoefels, Alan W. McLean, Barbara Franke, Huda Akil, Soumya Raychaudhuri, Ellen M. Wijsman, Vishwajit L. Nimgaonkar, Roy H. Perlis, Patrick J. McGrath, Susan L. Santangelo, William Coryell, Henrik B. Rasmussen, Weihua Guan, William Lawson, Elliot S. Gershon, Sean Ennis, Aiden Corvin, Allan H. Young, Thomas B. Barrett, Jonathan L. Haines, Douglas F. Levinson, Ana Miranda, Anil K. Malhotra, S. Hong Lee, Stan F. Nelson, Anthony J. Bailey, Patrick F. Sullivan, Dorothy E. Grice, Lefkos T. Middleton, Bertram Mueller-Myhsok, Michael R. Barnes, Adebayo Anjorin, O'Dushlaine, C, Rossin, L, Lee, Ph, Duncan, L, Parikshak, Nn, Newhouse, S, Ripke, S, Neale, Bm, Purcell, Sm, Posthuma, D, Nurnberger, Ji, Lee, Sh, Faraone, Sv, Perlis, Rh, Mowry, Bj, Thapar, A, Goddard, Me, Witte, J, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, Oa, Anjorin, A, Anney, R, Anttila, V, Arking, De, Asherson, P, Azevedo, Mh, Backlund, L, Badner, Ja, Bailey, Aj, Banaschewski, T, Barchas, Jd, Barnes, Mr, Barrett, Tb, Bass, N, Battaglia, A, Bauer, M, Bayés, M, Bellivier, F, Bergen, Se, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, Eb, Black, Dw, Blackwood, Dh, Bloss, C, Boehnke, M, Boomsma, Di, Breuer, R, Bruggeman, R, Cormican, P, Buccola, Ng, Buitelaar, Jk, Bunney, We, Buxbaum, Jd, Byerley, Wf, Byrne, Em, Caesar, S, Cahn, W, Cantor, Rm, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Mattheisen, M, Cloninger, Cr, Collier, Da, Cook, Eh, Coon, H, Cormand, B, Corvin, A, Coryell, Wh, Craig, Dw, Craig, Iw, Crosbie, J, Cuccaro, Ml, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, Ej, Degenhardt, F, Djurovic, S, Donohoe, Gj, Doyle, Ae, Duan, J, Dudbridge, F, Duketis, E, Ebstein, Rp, Edenberg, Hj, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, Ae, Ferrier, In, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, Nb, Freitag, Cm, Friedl, M, Frisén, L, Gallagher, L, Gejman, Pv, Georgieva, L, Gershon, E, Giegling, I, Gill, M, Gordon, Sd, Gordon-Smith, K, Green, Ek, Greenwood, Ta, Grice, De, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, Jl, Hakonarson, H, Hallmayer, J, Hamilton, Sp, Hamshere, Ml, Hansen, Tf, Hartmann, Am, Hautzinger, M, Heath, Ac, Henders, Ak, Herms, S, Hickie, Ib, Hipolito, M, Hoefels, S, Holsboer, F, Hoogendijk, Wj, Hottenga, Jj, Hultman, Cm, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, Eg, Jones, I, Jones, L, Tzeng, Jy, Kähler, Ak, Kahn, R, Kandaswamy, R, Keller, Mc, Kennedy, Jl, Kenny, E, Kent, L, Kim, Y, Kirov, Gk, Klauck, Sm, Klei, L, Knowles, Ja, Kohli, Ma, Koller, Dl, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landén, M, Längström, N, Lathrop, M, Lawrence, J, Lawson, Wb, Leboyer, M, Ledbetter, Dh, Lencz, T, Lesch, Kp, Levinson, Df, Lewis, Cm, Li, J, Lichtenstein, P, Lieberman, Ja, Lin, Dy, Linszen, Dh, Liu, C, Lohoff, Fw, Loo, Sk, Lord, C, Lowe, Jk, Lucae, S, Macintyre, Dj, Madden, Pa, Maestrini, E, Magnusson, Pk, Mahon, Pb, Maier, W, Malhotra, Ak, Mane, Sm, Martin, Cl, Martin, Ng, Matthews, K, Mattingsdal, M, Mccarroll, Sa, Mcghee, Ka, Mcgough, Jj, Mcgrath, Pj, Mcguffin, P, Mcinnis, Mg, Mcintosh, A, Mckinney, R, Mclean, Aw, Mcmahon, Fj, Mcmahon, Wm, Mcquillin, A, Medeiros, H, Medland, Se, Meier, S, Melle, I, Meyer, J, Middeldorp, Cm, Middleton, L, Milanova, V, Miranda, A, Monaco, A, Montgomery, Gw, Moran, Jl, Moreno-De-Luca, D, Morken, G, Morris, Dw, Morrow, Em, Moskvina, V, Muglia, P, Mühleisen, Tw, Muir, Wj, Müller-Myhsok, B, Murtha, M, Myers, Rm, Myin-Germeys, I, Neale, Mc, Nelson, Sf, Nievergelt, Cm, Nikolov, I, Nimgaonkar, V, Nolen, Wa, Nöthen, Mm, Nwulia, Ea, Nyholt, Dr, Oades, Rd, Olincy, A, Oliveira, G, Olsen, L, Ophoff, Ra, Osby, U, Owen, Mj, Palotie, A, Parr, Jr, Paterson, Ad, Pato, Cn, Pato, Mt, Penninx, Bw, Pergadia, Ml, Pericak-Vance, Ma, Pickard, B, Pimm, J, Piven, J, Potash, Jb, Poustka, F, Propping, P, Puri, V, Quested, Dj, Quinn, Em, Ramos-Quiroga, Ja, Rasmussen, Hb, Raychaudhuri, S, Rehnström, K, Reif, A, Ribasés, M, Rice, Jp, Rietschel, M, Roeder, K, Roeyers, H, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, Ar, Sanders, Sj, Santangelo, Sl, Sergeant, Ja, Schachar, R, Schalling, M, Schatzberg, Af, Scheftner, Wa, Schellenberg, Gd, Scherer, Sw, Schork, Nj, Schulze, Tg, Schumacher, J, Schwarz, M, Scolnick, E, Scott, Lj, Shi, J, Shilling, Pd, Shyn, Si, Silverman, Jm, Slager, Sl, Smalley, Sl, Smit, Jh, Smith, En, Sonuga-Barke, Ej, St Clair, D, State, M, Steffens, M, Steinhausen, Hc, Strauss, J, Strohmaier, J, Stroup, T, Sutcliffe, J, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, Rc, Todorov, Aa, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, Jc, Van Grootheest, G, Van Os, J, Vicente, A, Vieland, Vj, Vincent, Jb, Visscher, Pm, Walsh, Ca, Wassink, Th, Watson, Sj, Weissman, Mm, Werge, T, Wienker, Tf, Wijsman, Em, Willemsen, G, Williams, N, Willsey, Aj, Witt, Sh, Xu, W, Young, Ah, Yu, Tw, Zammit, S, Zandi, Pp, Zhang, P, Zitman, Fg, Zöllner, S, Devlin, B, Kelsoe, Jr, Sklar, P, Daly, Mj, O'Donovan, Mc, Craddock, N, Kendler, K, Weiss, La, Wray, Nr, Zhao, Z, Geschwind, Dh, Sullivan, Pf, Smoller, Jw, Holmans, Pa, Breen, G., Génétique de l'autisme = Genetics of Autism (NPS-01), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Human genetics, Psychiatry, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Gastroenterology & Hepatology, Hematology, University of St Andrews. School of Medicine, University of St Andrews. Institute of Behavioural and Neural Sciences, Psychiatrie & Neuropsychologie, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), RS: MHeNs - R2 - Mental Health, ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Universitat de Barcelona, Perceptual and Cognitive Neuroscience (PCN), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Complex Trait Genetics, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, LEARN! - Brain, learning and development, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), O'Dushlaine, Colm, Rossin, Lizzy, Lee, Phil H, Duncan, Laramie, Lee, S Hong, Breen, Gerome, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Network and Pathway Analysis Subgroup of the Psychiatric Genomics Consortium, and Myin-Germeys, Inez
Subjects: Netherlands Twin Register (NTR), Statistical methods, Autism, Medizin, LOCI, Genome-wide association study, heritability, Genome-wide association studies, Histones, Genètica mèdica, 0302 clinical medicine, Histone methylation, Databases, Genetic, 2.1 Biological and endogenous factors, Psychology, GWAS, Aetiology, Psychiatric genetics, R2C, bipolar disorder, Psychiatry, 0303 health sciences, Disorders, Loci, Depression, General Neuroscience, Mental Disorders, Medical genetics, METHYLATION, Brain, 3rd-DAS, Serious Mental Illness, Psychiatric Disorders, 3. Good health, Histone, Mental Health, Schizophrenia, Mental Disorder, Cognitive Sciences, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Promoters, BDC, BURDEN, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Human, Signal Transduction, medicine.medical_specialty, DISORDERS, Genomics, Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium, Burden, Biology, Methylation, Article, Biological pathway, PROMOTERS, 03 medical and health sciences, Databases, Genetic, medicine, Genetics, Humans, Genetic Predisposition to Disease, histone methylation, Bipolar disorder, Psiquiatria, AUTISM, 030304 developmental biology, Genetic association, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurology & Neurosurgery, Neuroscience (all), Human Genome, Neurosciences, medicine.disease, Brain Disorders, Good Health and Well Being, DE-NOVO MUTATIONS, Perturbações do Desenvolvimento Infantil e Saúde Mental, RC0321, Genome-wide Association Studies, De-novo mutations, major depression, Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: G.B. and S.N. acknowledge funding support for this work from the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. P.H.L. is supported by US National Institute of Mental Health (NIMH) grant K99MH101367. Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders. Postprint
Published: 2015

32. Genetic studies of body mass index yield new insights for obesity biology

Author: Locke, Adam E, Kahali, Bratati, Croteau-Chonka, Damien C, Doney, Alex S F, He, Bing, Heikkilä, Outi, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Eklund, Niina, Saraheimo, Markku, Sarti, Cinzia, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Estrada, Karol, Wadén, Johan, Gill, Geoffrey V, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Eury, Elodie, Ladenvall, Claes, Alhenc-Gelas, François, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Folkersen, Lasse, Möllsten, Anna, Cimponeriu, Dan, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Fraser, Ross M, Colhoun, Helen M, Panduru, Nicolae Mircea, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Garcia, Melissa E, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Geller, Frank, Willer, Cristen J, Schmidt, Ellen M, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Buchkovich, Martin L, Mora, Samia, Giedraitis, Vilmantas, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Chang, Hsing-Y, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Gigante, Bruna, Ferreira, Teresa, Fischer, Krista, Fontanillas, Pierre, Freitag, Daniel F, Gurdasani, Deepti, Heikkilä, Kauko, Hyppönen, Elina, Isaacs, Aaron, Jackson, Anne U, Esko, Tonu, Go, Alan S, Johansson, Åsa, Johnson, Toby, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Golay, Alain, Mihailov, Evelin, Montasser, May E, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Goodall, Alison H, Service, Susan K, Shah, Sonia, Shungin, Dmitry, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Thorleifsson, Gudmar, Gordon, Scott D, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Gorski, Mathias, Been, Latonya F, Bolton, Jennifer L, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doring, Angela, Elliott, Paul, Grabe, Hans-Jörgen, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hallmans, Göran, Hartikainen, Anna-Liisa, Hayward, Caroline, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Khaw, Kay-Tee, Kim, Eric, Grammer, Tanja B, Klopp, Norman, Komulainen, Pirjo, Kumari, Meena, Langenberg, Claudia, Lehtimaki, Terho, Lin, Shih-Yi, Lindstrom, Jaana, Loos, Ruth J F, Mach, François, McArdle, Wendy L, Gräßler, Jürgen, Meisinger, Christa, Mitchell, Braxton D, Muller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Grönberg, Henrik, Papamarkou, Theodore, Pomilla, Cristina, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Ridker, Paul M, Rivadeneira, Fernando, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Fall, Tove, Scharnagl, Hubert, Seeley, Janet, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, Tiret, Laurence, Uitterlinden, Andre G, van Pelt, L Joost, Vedantam, Sailaja, Gusto, Gaëlle, Wainwright, Nicholas, Wijmenga, Cisca, Wild, Sarah H, Willemsen, Gonneke, Wilsgaard, Tom, Wilson, James F, Young, Elizabeth H, Zhao, Jing Hua, Adair, Linda S, Arveiler, Dominique, Haessler, Jeffrey, Assimes, Themistocles L, Bandinelli, Stefania, Bennett, Franklyn, Bochud, Murielle, Boehm, Bernhard O, Boomsma, Dorret I, Borecki, Ingrid B, Bornstein, Stefan R, Bovet, Pascal, Burnier, Michel, Hall, Per, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chen, Yii-Der Ida, Collins, Francis S, Cooper, Richard S, Danesh, John, Dedoussis, George, de Faire, Ulf, Feranil, Alan B, Haller, Toomas, Ferrieres, Jean, Ferrucci, Luigi, Freimer, Nelson B, Gieger, Christian, Groop, Leif C, Gudnason, Vilmundur, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Hingorani, Aroon, Hallmans, Goran, Hofman, Albert, Hovingh, G Kees, Hsiung, Chao Agnes, Humphries, Steve E, Hunt, Steven C, Hveem, Kristian, Iribarren, Carlos, Jarvelin, Marjo-Riitta, Jula, Antti, Hartman, Catharina A, Kähönen, Mika, Kaprio, Jaakko, Kesäniemi, Antero, Kivimaki, Mika, Kooner, Jaspal S, Koudstaal, Peter J, Krauss, Ronald M, Kuh, Diana, Kuusisto, Johanna, Kyvik, Kirsten O, Hassinen, Maija, Laakso, Markku, Lakka, Timo A, Lind, Lars, Lindgren, Cecilia M, Martin, Nicholas G, März, Winfried, McCarthy, Mark I, McKenzie, Colin A, Meneton, Pierre, Metspalu, Andres, Moilanen, Leena, Morris, Andrew D, Munroe, Patricia B, Njølstad, Inger, Pedersen, Nancy L, Power, Chris, Pramstaller, Peter P, Price, Jackie F, Psaty, Bruce M, Quertermous, Thomas, Heard-Costa, Nancy L, Rauramaa, Rainer, Saleheen, Danish, Salomaa, Veikko, Sanghera, Dharambir K, Saramies, Jouko, Schwarz, Peter E H, Sheu, Wayne H-H, Shuldiner, Alan R, Siegbahn, Agneta, Spector, Tim D, Helmer, Quinta, Stefansson, Kari, Strachan, David P, Tayo, Bamidele O, Tremoli, Elena, Uusitupa, Matti, van Duijn, Cornelia M, Vollenweider, Peter, Wallentin, Lars, Wareham, Nicholas J, Hengstenberg, Christian, Whitfield, John B, Wolffenbuttel, Bruce H R, Ordovas, Jose M, Boerwinkle, Eric, Palmer, Colin N A, Thorsteinsdottir, Unnur, Chasman, Daniel I, Rotter, Jerome I, Franks, Paul W, Ripatti, Samuli, Holmen, Oddgeir, Cupples, L Adrienne, Sandhu, Manjinder S, Rich, Stephen S, Boehnke, Michael, Deloukas, Panos, Kathiresan, Sekar, Mohlke, Karen L, Ingelsson, Erik, Abecasis, Gonçalo R, Abecasis, Gonçalo, Hottenga, Jouke-Jan, Caulfield, Mark, Chasman, Dan, Ehret, Georg, Johnson, Andrew, Johnson, Louise, Larson, Martin, Levy, Daniel, James, Alan L, Munroe, Patricia, Newton-Cheh, Christopher, O'Reilly, Paul, Palmas, Walter, Psaty, Bruce, Rice, Kenneth, Smith, Albert, Snider, Harold, Tobin, Martin, Van Duijn, Cornelia, Jeff, Janina M, Verwoert, Germaine, Rice, Kenneth M, Johnson, Andrew D, Smith, Albert V, Tobin, Martin D, Verwoert, Germaine C, Hwang, Shih-Jen, Pihur, Vasyl, O'Reilly, Paul F, Amin, Najaf, Teumer, Alexander, Glazer, Nicole L, Launer, Lenore, Jolley, Jennifer, Aulchenko, Yurii, Heath, Simon, Sõber, Siim, Parsa, Afshin, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Juliusdottir, Thorhildur, Peden, John F, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N, Fava, Cristiano, Kinnunen, Leena, Fox, Ervin R, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Koenig, Wolfgang, Whincup, Peter H, Liu, Yongmei, Shi, Gang, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Nguyen, Khanh-Dung Hoang, Lehtimäki, Terho, Matullo, Giuseppe, Koskenvuo, Markku, Gaunt, Tom R, Onland-Moret, N Charlotte, Cooper, Matthew N, Platou, Carl G P, Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Kratzer, Wolfgang, Braund, Peter S, Kuznetsova, Tatiana, Uiterwaal, Cuno S P M, Adeyemo, Adebowale, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D, Laitinen, Jaana, Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C, Steinle, Nanette I, Grobbee, Diederick E, Arking, Dan E, Kardia, Sharon L, Morrison, Alanna C, Lamina, Claudia, Najjar, Samer, Hadley, David, Brown, Morris J, Connell, John M, Hingorani, Aroon D, Day, Ian N M, Lawlor, Debbie A, Beilby, John P, Lawrence, Robert W, Leander, Karin, Clarke, Robert, Collins, Rory, Hopewell, Jemma C, Ongen, Halit, Dreisbach, Albert W, Li, Yali, Young, J. H., Bis, Joshua C, Viikari, Jorma, Lee, Nanette R, Chen, Ming-Huei, Olden, Matthias, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Lichtner, Peter, Frayling, Timothy M, Islam, Muhammad, Jafar, Tazeen H, Erdmann, Jeanette, Kulkarni, Smita R, Grässler, Jürgen, Howard, Philip, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Weder, Alan B, Lindström, Jaana, Sun, Yan V, Bergman, Richard N, Scott, Laura J, Stringham, Heather M, Peltonen, Leena, Vartiainen, Erkki, Brand, Stefan-Martin, Kutalik, Zoltán, Lo, Ken Sin, Staessen, Jan A, Wang, Thomas J, Burton, Paul R, Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K, Rudock, Megan E, Lobbens, Stéphane, Heckbert, Susan R, Smith, Nicholas L, Wiggins, Kerri L, Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairajan, Tripathy, Vikal, Lorbeer, Roberto, Langefeld, Carl D, Rosengren, Annika, Thelle, Dag S, Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Salako, Tunde, Iwai, Naoharu, Lu, Yingchang, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H-Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, James, Sehmi, Joban S, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Raffel, Leslie J, Yao, Jie, O'Donnell, Chris, Schwartz, Stephen M, Ikram, M Arfan, Longstreth, W. T., Mosley, Thomas H, Seshadri, Sudha, Mahajan, Anubha, Shrine, Nick R G, Wain, Louise V, Morken, Mario A, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A, Rasheed, Asif, Goel, Anuj, Watkins, Hugh, Bakker, Stephan J L, van Gilst, Wiek H, Janipalli, Charles S, Mani, K Radha, Yajnik, Chittaranjan S, McLachlan, Stela, Mattace-Raso, Francesco U S, Oostra, Ben A, Demirkan, Ayse, Lakatta, Edward G, Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J, Menni, Cristina, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Ong, Rick Twee-Hee, Dörr, Marcus, Kroemer, Heyo K, Völker, Uwe, Völzke, Henry, Galan, Pilar, Merger, Sigrun, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Zhai, Guangju, Meschia, James F, Nalls, Michael A, Sharma, Pankaj, Terzic, Janos, Kumar, M J Kranthi, Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E, Fowkes, F Gerald R, Charchar, Fadi J, Guo, Xiuqing, Milani, Lili, Rotimi, Charles, Bots, Michiel L, Brand, Eva, Samani, Nilesh J, Polasek, Ozren, Talmud, Philippa J, Nyberg, Fredrik, Laan, Maris, Moayyeri, Alireza, Palmer, Lyle J, van der Schouw, Yvonne T, Casas, Juan P, Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K, Wong, Tien Y, Tai, E Shyong, Monda, Keri L, Rao, Dabeeru C, Morris, Richard W, Dominiczak, Anna F, Marmot, Michael G, Miki, Tetsuro, Chandak, Giriraj R, Coresh, Josef, Navis, Gerjan, Han, Bok-Ghee, Zhu, Xiaofeng, Melander, Olle, Gyllensten, Ulf B, Mulas, Antonella, Wright, Alan F, Farrall, Martin, Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J G, Altshuler, David, Müller, Gabriele, Rettig, Rainer, Uda, Manuela, Witteman, Jacqueline C M, Vasan, Ramachandran S, Larson, Martin G, Järvelin, Marjo-Riitta, Musk, Arthur W, Caulfield, Mark J, Alizadeh, Behrooz Z, de Boer, Rudolf A, Mägi, Reedik, Boezen, H Marike, Bruinenberg, Marcel, Franke, Lude, Hillege, Hans L, van der Klauw, Melanie M, Ormel, Johan, Postma, Dirkje S, Rosmalen, Judith G M, Nöthen, Markus M, Slaets, Joris P, Stolk, Ronald P, Scott, Robert A, Lagou, Vasiliki, Welch, Ryan P, Wheeler, Eleanor, Rehnberg, Emil, Rasmussen-Torvik, Laura J, Yengo, Loïc, Lecoeur, Cecile, Pilz, Stefan, Johnson, Paul C D, Jukema, J Wouter, Verweij, Niek, Rayner, Nigel W, Sennblad, Bengt, Salo, Perttu, Timpson, Nicholas J, Evans, David M, St Pourcain, Beate, Andrews, Jeanette S, Renstrom, Frida, Hui, Jennie, Bielak, Lawrence F, Zhao, Wei, Horikoshi, Momoko, Navarro, Pau, Esko, Tönu, Raychaudhuri, Soumya, Chen, Han, Morris, Andrew P, Ried, Janina S, Robertson, Neil, Rybin, Denis, Liu, Ching-Ti, Willems, Sara M, Chines, Peter S, Kang, Hyun Min, Song, Kijoung, Ripke, Stephan, An, Ping, Franco-Cereceda, Anders, Marullo, Letizia, Jansen, Hanneke, Robertson, Neil R, Oldehinkel, Albertine J, Pankow, James S, North, Kari E, Forouhi, Nita G, Edkins, Sarah, Varga, Tibor V, Oksa, Heikki, Randall, Joshua C, Rose, Lynda M, Antonella, Mulas, Trompet, Stella, Ford, Ian, Kong, Augustine, Herder, Christian, Antti, Jula, Small, Kerrin, Miljkovic, Iva, Atalay, Mustafa, Kiess, Wieland, Smit, Johannes H, Campbell, Susan, Scholtens, Salome, Fowkes, Gerard R, Kovacs, Peter, Zemunik, Tatijana, Basart, Hanneke V, Rathmann, Wolfgang, Schumacher, Fredrick R, Maerz, Winfried, Peters, Annette, Province, Michael A, Hastie, Nicholas D, Scott, William R, Stumvoll, Michael, Waterworth, Dawn M, Watanabe, Richard M, de Geus, Eco J C, Seufferlein, Thomas, Penninx, Brenda W, Shi, Jianxin, Dedoussis, George V, Smith, Albert Vernon, Toenjes, Anke, Peyser, Patricia A, Körner, Antje, Smolonska, Joanna, Winkler, Thomas W, Stanton, Alice V, Keinanen-Kiukaanniemi, Sirkka M, Saaristo, Timo E, Dupuis, Josée, Sattar, Naveed, Steinthorsdottir, Valgerdur, Cucca, Francesco, Balkau, Beverley, Froguel, Philippe, Bouatia-Naji, Nabila, Meigs, James B, Purcell, Shaun, Musunuru, Kiran, Ardissino, Diego, Mannucci, Pier M, Anand, Sonia, Engert, James C, Schunkert, Heribert, Sundström, Johan, Morgan, Thomas, Spertus, John A, Stoll, Monika, Girelli, Domenico, McKeown, Pascal P, Patterson, Chris C, Siscovick, David S, O'Donnell, Christopher J, Swertz, Morris A, Merlini, Pier Angelica, Berzuini, Carlo, Bernardinelli, Luisa, Peyvandi, Flora, Tubaro, Marco, Celli, Patrizia, Ferrario, Maurizio, Fetiveau, Raffaela, Marziliano, Nicola, Casari, Giorgio, Galli, Michele, Ribichini, Flavio, Rossi, Marco, Syvänen, Ann-Christine, Bernardi, Francesco, Zonzin, Pietro, Piazza, Alberto, Yee, Jean, Friedlander, Yechiel, Marrugat, Jaume, Tan, Sian-Tsung, Subirana, Isaac, Sala, Joan, Ramos, Rafael, Williams, Gordon, Nathan, David M, MacRae, Calum A, Havulinna, Aki S, Berglund, Goran, Asselta, Rosanna, Duga, Stefano, Berndt, Sonja I, Wood, Andrew R, Thorand, Barbara, Spreafico, Marta, Daly, Mark J, Nemesh, James, Korn, Joshua M, McCarroll, Steven A, Surti, Aarti, Gianniny, Lauren, Mirel, Daniel, Parkin, Melissa, Tyrer, Jonathan P, Burtt, Noel, Gabriel, Stacey B, Thompson, John R, Wright, Benjamin J, Balmforth, Anthony J, Ball, Stephen G, Hall, Alistair S, Schunkert, I Heribert, Uh, Hae-Won, Linsel-Nitschke, Patrick, Lieb, Wolfgang, Ziegler, Andreas, König, Inke R, Fischer, Marcus, Stark, Klaus, Grosshennig, Anika, Preuss, Michael, Vandenput, Liesbeth, Schreiber, Stefan, Ouwehand, Willem, Scholz, Michael, Cambien, Francois, Verhulst, Frank C, Goodall, Alison, Li, Mingyao, Chen, Zhen, Wilensky, Robert, Matthai, William, Qasim, Atif, Hakonarson, Hakon H, Devaney, Joe, Burnett, Mary-Susan, Vermeulen, Sita H, Pichard, Augusto D, Kent, Kenneth M, Satler, Lowell, Lindsay, Joseph M, Waksman, Ron, Knouff, Christopher W, Walker, Max C, Scheffold, Thomas, Berger, Klaus, Huge, Andreas, Martinelli, Nicola, Olivieri, Oliviero, Corrocher, Roberto, Vonk, Judith M, Hólm, Hilma, Workalemahu, Tsegaselassie, Warren, Helen R, Xie, Changchun, Siscovick, David, Waterworth, Dawn, Ahmadi, Kourosh R, Ainali, Chrysanthi, Barrett, Amy, Bataille, Veronique, Weedon, Michael N, Bell, Jordana T, Buil, Alfonso, Dermitzakis, Emmanouil T, Dimas, Antigone S, Durbin, Richard, Glass, Daniel, Grundberg, Elin, Hassanali, Neelam, Hedman, Åsa K, Wilkens, Lynne R, Ingle, Catherine, Keildson, Sarah, Knowles, David, Krestyaninova, Maria, Lowe, Christopher E, Meduri, Eshwar, di Meglio, Paola, Min, Josine L, Willenborg, Christina, Montgomery, Stephen B, Nestle, Frank O, Nica, Alexandra C, Nisbet, James, O'Rahilly, Stephen, Parts, Leopold, Potter, Simon, Sekowska, Magdalena, Shin, So-Youn, Small, Kerrin S, Surdulescu, Gabriela, Travers, Mary E, Tsaprouni, Loukia, Tsoka, Sophia, Wilk, Alicja, Yang, Tsun-Po, Zondervan, Krina T, Matise, Tara, Wojczynski, Mary K, Buyske, Steve, Higashio, Julia, Williams, Rasheeda, Nato, Andrew, Ambite, Jose Luis, Deelman, Ewa, Manolio, Teri, Hindorff, Lucia, Heiss, Gerardo, Taylor, Kira, Franceschini, Nora, Avery, Christy, Graff, Misa, Lin, Danyu, Quibrera, Miguel, Cochran, Barbara, Kao, Linda, Umans, Jason, Cole, Shelley, MacCluer, Jean, Person, Sharina, Pankow, James, Gross, Myron, Fornage, Myriam, Durda, Peter, Jenny, Nancy, Patsy, Bruce, Arnold, Alice, Zhang, Qunyuan, Buzkova, Petra, Crawford, Dana, Haines, Jonathan, Murdock, Deborah, Glenn, Kim, Brown-Gentry, Kristin, Thornton-Wells, Tricia, Dumitrescu, Logan, Jeff, Janina, Bush, William S, Faul, Jessica D, Study, LifeLines Cohort, Mitchell, Sabrina L, Goodloe, Robert, Wilson, Sarah, Boston, Jonathan, Malinowski, Jennifer, Restrepo, Nicole, Oetjens, Matthew, Fowke, Jay, Zheng, Wei, Spencer, Kylee, Brennan, Eoin P, Ritchie, Marylyn, Pendergrass, Sarah, Le Marchand, Loïc, Wilkens, Lynne, Park, Lani, Tiirikainen, Maarit, Kolonel, Laurence, Lim, Unhee, Cheng, Iona, Wang, Hansong, Choi, Murim, Shohet, Ralph, Haiman, Christopher, Stram, Daniel, Henderson, Brian, Monroe, Kristine, Schumacher, Fredrick, Kooperberg, Charles, Peters, Ulrike, Anderson, Garnet, Carlson, Chris, Dastani, Zari, Prentice, Ross, LaCroix, Andrea, Wu, Chunyuan, Carty, Cara, Gong, Jian, Rosse, Stephanie, Young, Alicia, Haessler, Jeff, Kocarnik, Jonathan, Lin, Yi, Drong, Alexander W, Jackson, Rebecca, Duggan, David, Kuller, Lew, Stolk, Lisette, Perry, John R B, He, Chunyan, Sulem, Patrick, Barbalic, Maja, Eriksson, Per, Broer, Linda, Byrne, Enda M, Ernst, Florian, Gudbjartsson, Daniel F, Kraft, Peter, McArdle, Patick F, Porcu, Eleonora, van Wingerden, Sophie, Zhuang, Wei V, Albrecht, Eva, Lauc, Lovorka Barac, Gådin, Jesper R, Boban, Mladen, Broekmans, Frank J, Burri, Andrea, Chanock, Stephen J, Chen, Constance, Cornelis, Marilyn C, Corre, Tanguy, Gharavi, Ali G, Coviello, Andrea D, d'Adamo, Pio, Davies, Gail, Deary, Ian J, Dedoussis, George V Z, Deloukas, Panagiotis, Ebrahim, Shah, Eiriksdottir, Gudny, Goddard, Michael E, Eriksson, Johan G, Fauser, Bart C J M, Ferreli, Liana, Folsom, Aaron R, Gasparini, Paolo, Smith, Jennifer A, Handsaker, Robert E, Glazer, Nicole, Hankinson, Susan E, Hass, Merli, Heath, Andrew C, Huang, Jinyan, Janssens, A Cecile J W, Karasik, David, Kardia, Sharon L R, Keyzer, Jules, Kiel, Douglas P, Kolcic, Ivana, Lahti, Jari, Lai, Sandra, Karpe, Fredrik, Laisk, Triin, Laven, Joop S E, Liu, Jianjun, Lopez, Lorna M, Louwers, Yvonne V, Marongiu, Mara, Klaric, Irena Martinovic, Masciullo, Corrado, McKnight, Barbara, Medland, Sarah E, Melzer, David, Newman, Anne B, Nyholt, Dale R, Paré, Guillaume, Peeters, Petra H M, Pistis, Giorgio, Plump, Andrew S, Pop, Victor J M, Räikkönen, Katri, Kiryluk, Krzysztof, Sala, Cinzia, Salumets, Andres, Kubo, Michiaki, Stacey, Simon N, Starr, John M, Stathopoulou, Maria G, Styrkarsdottir, Unnur, Tenesa, Albert, Toniolo, Daniela, Tryggvadottir, Laufey, Tsui, Kim, Ulivi, Sheila, van Dam, Rob M, van Gils, Carla H, van Nierop, Peter, Vink, Jacqueline M, Visscher, Peter M, Voorhuis, Marlies, Liang, Liming, Waeber, Gérard, Wallaschofski, Henri, Wichmann, H Erich, Widen, Elisabeth, Wijnands-van Gent, Colette J M, Yerges-Armstrong, Laura M, Lifton, Richard P, Zgaga, Lina, Zillikens, M Carola, Zygmunt, Marek, Arnold, Alice M, Buring, Julie E, Crisponi, Laura, Demerath, Ellen W, Ma, Baoshan, Hu, Frank B, Hunter, David J, Launer, Lenore J, Montgomery, Grant W, Schlessinger, David, Streeten, Elizabeth A, Uitterlinden, André G, Murray, Anna, Murabito, Joanne M, McKnight, Amy J, Visser, Jenny A, Lunetta, Kathryn L, Elks, Cathy E, Cousminer, Diana L, Feenstra, Bjarke, Koller, Daniel L, Lin, Peng, Moffatt, Miriam F, McArdle, Patrick F, van Wingerden, Sophie W, Smith, Erin N, Ulivi, Shelia, Warrington, Nicole M, Alavere, Helen, Barroso, Ines, Berenson, Gerald S, Blackburn, Hannah, Busonero, Fabio, Chen, Wei, Nicholson, George, Couper, David, Döring, Angela, Easton, Douglas F, Eriksson, Johan, Foroud, Tatiana, Okada, Yukinori, Hernandez, Dena G, Kilpeläinen, Tuomas O, Li, Shengxu, Dorajoo, Rajkumar, Melbye, Mads, Murray, Jeffrey C, Murray, Sarah S, Nelis, Mari, Reinmaa, Eva, Ness, Andrew R, Northstone, Kate, Peacock, Munro, Salem, Rany M, Pennell, Craig E, Pharoah, Paul, Rafnar, Thorunn, Rice, John P, Ring, Susan M, Sandholm, Niina, Schork, Nicholas J, Segrè, Ayellet V, Sovio, Ulla, Srinivasan, Sathanur R, Tammesoo, Mar-Liis, Tikkanen, Emmi, Tyrer, Jonathon, van Meurs, Joyve B J, Waeber, Gerard, Takahashi, Atsushi, Young, Lauren, Zhuang, Wei Vivian, Bierut, Laura J, Boyd, Heather A, Tanaka, Toshihiro, Econs, Michael J, van 't Hooft, Ferdinand M, Vinkhuyzen, Anna A E, Westra, Harm-Jan, Consortium, ADIPOGen, Group, AGEN-BMI Working, Consortium, CARDIOGRAMplusC4D, Consortium, CKDGen, GLGC, ICBP, Fehrmann, Rudolf, Investigators, MAGIC, Consortium, MuTHER, Consortium, MIGen, Consortium, PAGE, Consortium, ReproGen, Consortium, GENIE, Consortium, International Endogene, Beilby, John, Blangero, John, Karjalainen, Juha, Crawford, Dana C, Cusi, Daniele, den Ruijter, Hester M, Erbel, Raimund, Justice, Anne E, Felix, Stephan B, Ferrannini, Ele, Ferrières, Jean, Franco, Oscar H, Gansevoort, Ron T, Gejman, Pablo V, Gottesman, Omri, Hattersley, Andrew T, Hindorff, Lucia A, Homuth, Georg, Jacobs, Kevin B, Anderson, Denise, Jöckel, Karl-Heinz, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M, Kiemeney, Lambertus A, Knekt, Paul, Beekman, Marian, Kraja, Aldi T, Marchand, Loic Le, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C, Moll, Frans L, Ohlsson, Claes, Madden, Pamela A F, Pasterkamp, Gerard, Buyske, Steven, Qi, Lu, Raitakari, Olli T, Rankinen, Tuomo, Rao, D. C., Rice, Treva K, Rioux, John D, Ritchie, Marylyn D, Sarzynski, Mark A, Sever, Peter, Sinisalo, Juha, Deng, Guohong, Strauch, Konstantin, Tönjes, Anke, Trégouët, David-Alexandre, Tremblay, Angelo, Virtamo, Jarmo, Vohl, Marie-Claude, Pers, Tune H, Witteman, Jacqueline C, Amouyel, Philippe, Asselbergs, Folkert W, Bottinger, Erwin P, Bouchard, Claude, Cauchi, Stéphane, de Bakker, Paul I W, Haiman, Christopher A, Kaplan, Robert C, Moebus, Susanne, Pérusse, Louis, Schadt, Eric E, Slagboom, P Eline, Walker, Mark, Weir, David R, Zanen, Pieter, Fox, Caroline S, Heid, Iris M, Scherag, André, Kristiansson, Kati, Speliotes, Elizabeth K, Day, Felix R, Goldstein, Benjamin A, Cazier, Jean-Baptiste, Lotay, Vaneet, Ho, Weang K, Eriksson, Niclas, Lundmark, Per, Rafelt, Suzanne, Leach, Irene Mateo, Van Zuydam, Natalie, Medina-Gomez, Carolina, Burgdorf, Christof, Claudi-Boehm, Simone, Cox, David, El Mokhtari, NourEddine, Hager, Jörg, Hunt, Sarah E, Kang, Hyun M, Kessler, Thorsten, Knowles, Joshua W, Kolovou, Genovefa, Langford, Cordelia, Lokki, Marja-Liisa, Lundmark, Anders, Maouche, Seraya, Nikus, Kjell, Rayner, N William, Pasko, Dorota, Rosinger, Silke, Rubin, Diana, Rumpf, Moritz P, Schäfer, Arne, Sivananthan, Mohan, Stewart, Alexandre F R, Thorgeirsson, Gudmundur, Pechlivanis, Sonali, van der Schoot, C Ellen, Wagner, Peter J, Wells, George A, Wild, Philipp S, Tsun-Po, Yang, Basart, Hanneke, Powell, Corey, Peters, Marjolein J, Cupples, Adrienne L, Diemert, Patrick, Evans, Alun, Ferrario, Marco M, Gauguier, Dominique, Gudnason, Villi, Hazen, Stanley L, Jang, Yangsoo, Kee, Frank, Kim, Hyo-Soo, Kuulasmaa, Kari, Laaksonen, Reijo, Lee, Ji-Young, Ouwehand, Willem H, Parish, Sarah, Park, Jeong E, Schadt, Eric, Shah, Svati H, Wareham, Nicholas, Zimmermann, Martina E, Nieminen, Markku S, Sung, Yun Ju, Pastinen, Tomi, Zalloua, Pierre A, Blankenberg, Stefan S, O'Donnell, Christopher, Roberts, Robert, Garnaas, Maija, Böger, Carsten A, Fuchsberger, Christian, Tin, Adrienne, Taliun, Daniel, Li, Man, van der Laan, Sander W, Gao, Xiaoyi, Yang, Qiong, Hundertmark, Claudia, Foster, Meredith C, O'Seaghdha, Conall M, van Setten, Jessica, Struchalin, Maksim, Li, Guo, Gierman, Hinco J, Feitosa, Mary, Atkinson, Elizabeth J, Lohman, Kurt, Van Vliet-Ostaptchouk, Jana V, Chouraki, Vincent, Holliday, Elizabeth G, Sorice, Rossella, Kutalik, Zoltan, Wang, Zhaoming, Deshmukh, Harshal, Chu, Audrey Y, Murgia, Federico, Imboden, Medea, Kollerits, Barbara, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, de Andrade, Mariza, Turner, Stephen T, Ding, Jingzhong, Freedman, Barry I, Minelli, Cosetta, Wheeler, Heather E, Zaboli, Ghazal, Ellinghaus, David, Nöthlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Endlich, Karlhans, Nauck, Matthias, Stracke, Sylvia, Ärnlöv, Johan, Aulchenko, Yurii S, Hastie, Nick, Arscott, Gillian M, Helmer, Catherine, Wang, Jie Jin, Ruggiero, Daniela, Nikopensius, Tiit, Province, Michael, Ketkar, Shamika, Attwood, Antony P, Colhoun, Helen, Doney, Alex, Robino, Antonietta, Giulianini, Franco, Krämer, Bernhard K, Portas, Laura, Buckley, Brendan M, Adam, Martin, Thun, Gian-Andri, Paulweber, Bernhard, Haun, Margot, Metzger, Marie, Mitchell, Paul, Ciullo, Marina, Kim, Stuart K, Palmer, Colin, Pirastu, Mario, Probst-Hensch, Nicole M, Kronenberg, Florian, Bas, Isabelita N, Schmidt, Reinhold, Borecki, Ingrid, Curhan, Gary C, Bellis, Claire, Franke, Andre, Ridker, Paul, Bennett, Amanda J, Goessling, Wolfram, Kao, W H Linda, Berne, Christian, de Boer, Ian H, Peralta, Carmen A, Blagieva, Roza, Akylbekova, Ermeg, Kramer, Holly, Blüher, Matthias, Böhringer, Stefan, Egan, Josephine, Reilly, Muredach, Townsend, Raymond R, Lumley, Thomas, Kestenbaum, Bryan, Haritunians, Talin, Yang, Jian, Böttcher, Yvonne, Lu, Xiaoning, Leak, Tennille S, Aasarød, Knut, Skorpen, Frank, Baumert, Jens, Devuyst, Olivier, Mychaleckyj, Josyf C, Kedenko, Lyudmyla, Coassin, Stefan, Caspersen, Ida H, Curhan, Gary, Hallan, Stein, Shlipak, Michael G, Kao, W. H. L., Anderson, Carl A, Daw, E Warwick, Guo, Qun, Henders, Anjali K, Lambert, Ann, Lee, Sang Hong, Kennedy, Stephen H, Macgregor, Stuart, Missmer, Stacey A, de Craen, Anton J M, Painter, Jodie N, Roseman, Fenella, Treloar, Susan A, Wallace, Leanne, Delgado, Graciela, McKnight, Amy Jayne, Forsblom, Carol, Isakova, Tamara, McKay, Gareth J, Williams, Winfred W, Sadlier, Denise M, Mäkinen, Ville-Petteri, Swan, Elizabeth J, Palmer, Cameron, Boright, Andrew P, Ahlqvist, Emma, Deshmukh, Harshal A, Keller, Benjamin J, Huang, Huateng, Ahola, Aila, Fagerholm, Emma, Gordin, Daniel, Harjutsalo, Valma, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Epidemiology, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Obstetrics & Gynecology, Locke, Adam E, Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltán, Luan, Jian'An, Mägi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Zhao, Jing Hua, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Åsa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Leach, Irene Mateo, Medina Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stančáková, Alena, Strawbridge, Rona J., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Van Der Laan, Sander W., Van Setten, Jessica, Van Vliet Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blüher, Matthia, Böhringer, Stefan, Bonnycastle, Lori L., Böttcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Chen, Yii Der Ida, Clarke, Robert, Daw, E. Warwick, De Craen, Anton J. M., Delgado, Graciela, Dimitriou, Maria, Doney, Alex S. F., Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M., Garcia, Melissa E., Geller, Frank, Giedraitis, Vilmanta, Gigante, Bruna, Go, Alan S., Golay, Alain, Goodall, Alison H., Gordon, Scott D., Gorski, Mathia, Grabe, Hans Jörgen, Grallert, Harald, Grammer, Tanja B., Gräßler, Jürgen, Grönberg, Henrik, Groves, Christopher J., Gusto, Gaëlle, Haessler, Jeffrey, Hall, Per, Haller, Tooma, Hallmans, Goran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heard Costa, Nancy L., Helmer, Quinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke Jan, James, Alan L., Jeff, Janina M., Johansson, Åsa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lar, Lindström, Jaana, Lo, Ken Sin, Lobbens, Stéphane, Lorbeer, Roberto, Lu, Yingchang, Mach, Françoi, Magnusson, Patrik K. E., Mahajan, Anubha, Mcardle, Wendy L., Mclachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L., Morken, Mario A., Mulas, Antonella, Müller, Gabriele, Müller Nurasyid, Martina, Musk, Arthur W., Nagaraja, Ramaiah, Nöthen, Markus M., Nolte, Ilja M., Pilz, Stefan, Rayner, Nigel W., Renstrom, Frida, Rettig, Rainer, Ried, Janina S., Ripke, Stephan, Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R., Scott, William R., Seufferlein, Thoma, Shi, Jianxin, Smith, Albert Vernon, Smolonska, Joanna, Stanton, Alice V., Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M., Sundström, Johan, Swertz, Morris A., Swift, Amy J., Syvänen, Ann Christine, Tan, Sian Tsung, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P., Uh, Hae Won, Vandenput, Liesbeth, Verhulst, Frank C., Vermeulen, Sita H., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Warren, Helen R., Waterworth, Dawn, Weedon, Michael N., Wilkens, Lynne R., Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Wright, Alan F., Zhang, Qunyuan, Brennan, Eoin P., Choi, Murim, Dastani, Zari, Drong, Alexander W., Eriksson, Per, Franco Cereceda, Ander, Gådin, Jesper R., Gharavi, Ali G., Goddard, Michael E., Handsaker, Robert E., Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong Young, Liang, Liming, Lifton, Richard P., Ma, Baoshan, Mccarroll, Steven A., Mcknight, Amy J., Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Okada, Yukinori, Perry, John R. B., Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Scott, Robert A., Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, Va't Hooft, Ferdinand M., Vinkhuyzen, Anna A. E., Westra, Harm Jan, Zheng, Wei, Zondervan, Krina T., Heath, Andrew C., Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J., Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Crawford, Dana C., Cupples, L. Adrienne, Cusi, Daniele, Danesh, John, De Faire, Ulf, Den Ruijter, Hester M., Dominiczak, Anna F., Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G., Farrall, Martin, Felix, Stephan B., Ferrannini, Ele, Ferrières, Jean, Ford, Ian, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Alistair S., Harris, Tamara B., Hattersley, Andrew T., Hicks, Andrew A., Hindorff, Lucia A., Hingorani, Aroon D., Hofman, Albert, Homuth, Georg, Hovingh, G. Kee, Humphries, Steve E., Hunt, Steven C., Hyppönen, Elina, Illig, Thoma, Jacobs, Kevin B., Jarvelin, Marjo Riitta, Jöckel, Karl Heinz, Johansen, Berit, Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti M., Kaprio, Jaakko, Kastelein, John J. P., Keinanen Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Knekt, Paul, Kooner, Jaspal S., Kooperberg, Charle, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C., Mckenzie, Colin A., Mcknight, Barbara, Moll, Frans L., Morris, Andrew D., Morris, Andrew P., Murray, Jeffrey C., Nelis, Mari, Ohlsson, Clae, Oldehinkel, Albertine J., Ong, Ken K., Madden, Pamela A. F., Pasterkamp, Gerard, Peden, John F., Peters, Annette, Postma, Dirkje S., Pramstaller, Peter P., Price, Jackie F., Qi, Lu, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Rioux, John D., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schunkert, Heribert, Schwarz, Peter E. H., Sever, Peter, Shuldiner, Alan R., Sinisalo, Juha, Stolk, Ronald P., Strauch, Konstantin, Tönjes, Anke, Trégouët, David Alexandre, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie Claude, Völker, Uwe, Waeber, Gérard, Willemsen, Gonneke, Witteman, Jacqueline C., Zillikens, M. Carola, Adair, Linda S., Amouyel, Philippe, Asselbergs, Folkert W., Assimes, Themistocles L., Bochud, Murielle, Boehm, Bernhard O., Boerwinkle, Eric, Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Cauchi, Stéphane, Chambers, John C., Chanock, Stephen J., Cooper, Richard S., De Bakker, Paul I. W., Dedoussis, George, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Groop, Leif C., Haiman, Christopher A., Hamsten, Ander, Hui, Jennie, Hunter, David J., Hveem, Kristian, Kaplan, Robert C., Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G., März, Winfried, Melbye, Mad, Metspalu, Andre, Moebus, Susanne, Munroe, Patricia B., Njolstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Marku, Pérusse, Loui, Peters, Ulrike, Power, Chri, Quertermous, Thoma, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sattar, Naveed, Schadt, Eric E., Schlessinger, David, Slagboom, P. Eline, Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G., Uusitupa, Matti, Van Der Harst, Pim, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wichmann, H. Erich, Wilson, James F., Zanen, Pieter, Borecki, Ingrid B., Deloukas, Pano, Fox, Caroline S., Heid, Iris M., O'Connell, Jeffrey R., Strachan, David P., Stefansson, Kari, Van Duijn, Cornelia M., Abecasis, Goncalo R., Franke, Lude, Frayling, Timothy M., Mccarthy, Mark I., Visscher, Peter M., Scherag, André, Willer, Cristen J., Boehnke, Michael, Mohlke, Karen L., Lindgren, Cecilia M., Beckmann, Jacques S., Barroso, Inê, North, Kari E., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F., Speliotes, Elizabeth K., D'Adamo, ADAMO PIO, Gasparini, Paolo, LifeLines Cohort Study, ADIPOGen Consortium, AGEN-BMI Working Group, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, MAGIC Investigators, MuTHER Consortium, MIGen Consortium, PAGE Consortium, ReproGen Consortium, GENIE Consortium, International Endogene Consortium, GLGC, ICBP, Deloukas, P., Kanoni, S., Willenborg, C., Farrall, M., Assimes, TL., Thompson, JR., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, BA., Stirrups, K., König, IR., Cazier, JB., Johansson£££Åsa£££ Å., Hall, AS., Lee, JY., Willer, CJ., Chambers, JC., Esko£££Tõnu£££ T., Folkersen, L., Goel, A., Grundberg, E., Havulinna, AS., Ho, WK., Hopewell, JC., Eriksson, N., Kleber, ME., Kristiansson, K., Lundmark, P., Lyytikäinen, LP., Rafelt, S., Shungin, D., Strawbridge, RJ., Thorleifsson, G., Tikkanen, E., Van Zuydam, N., Voight, BF., Waite, LL., Zhang, W., Ziegler, A., Absher, D., Altshuler, D., Balmforth, AJ., Barroso£££Inês£££ I., Braund, PS., Burgdorf, C., Claudi-Boehm, S., Cox, D., Dimitriou, M., Do, R., Doney, AS., El Mokhtari, N., Eriksson, P., Fischer, K., Fontanillas, P., Franco-Cereceda, A., Gigante, B., Groop, L., Gustafsson, S., Hager, J., Hallmans, G., Han, BG., Hunt, SE., Kang, HM., Illig, T., Kessler, T., Knowles, JW., Kolovou, G., Kuusisto, J., Langenberg, C., Langford, C., Leander, K., Lokki, ML., Lundmark, A., McCarthy, MI., Meisinger, C., Melander, O., Mihailov, E., Maouche, S., Morris, AD., Müller-Nurasyid, M., Nikus, K., Peden, JF., Rayner, NW., Rasheed, A., Rosinger, S., Rubin, D., Rumpf, MP., Schäfer, A., Sivananthan, M., Song, C., Stewart, AF., Tan, ST., Thorgeirsson, G., van der Schoot CE., Wagner, PJ., Wells, GA., Wild, PS., Tsun-Po, Y., Amouyel, P., Arveiler, D., Basart, H., Boehnke, M., Boerwinkle, E., Brambilla, P., Cambien, F., Cupples, AL., de Faire, U., Dehghan, A., Diemert, P., Epstein, SE., Evans, A., Ferrario, MM., Ferrières, J., Gauguier, D., Go, AS., Goodall, AH., Gudnason, V., Hazen, SL., Holm, H., Iribarren, C., Jang, Y., Kähönen, M., Kee, F., Kim, HS., Klopp, N., Koenig, W., Kratzer, W., Kuulasmaa, K., Laakso, M., Laaksonen, R., Lind, L., Ouwehand, WH., Parish, S., Park, JE., Pedersen, NL., Peters, A., Quertermous, T., Rader, DJ., Salomaa, V., Schadt, E., Shah, SH., Sinisalo, J., Stark, K., Stefansson, K., Trégouët, DA., Virtamo, J., Wallentin, L., Wareham, N., Zimmermann, ME., Nieminen, MS., Hengstenberg, C., Sandhu, MS., Pastinen, T., Syvänen, AC., Hovingh, GK., Dedoussis, G., Franks, PW., Lehtimäki, T., Metspalu, A., Zalloua, PA., Siegbahn, A., Schreiber, S., Ripatti, S., Blankenberg, SS., Perola, M., Clarke, R., Boehm, BO., O'Donnell, C., Reilly, MP., März, W., Collins, R., Kathiresan, S., Hamsten, A., Kooner, JS., Thorsteinsdottir, U., Danesh, J., Palmer, CN., Roberts, R., Watkins, H., Schunkert, H., Samani, NJ., Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, CA., Fuchsberger, C., Olden, M., Chen, MH., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, MC., O'Seaghdha, CM., Glazer, N., Isaacs, A., Liu, CT., Smith, AV., O'Connell, JR., Struchalin, M., Tanaka, T., Li, G., Johnson, AD., Gierman, HJ., Feitosa, M., Hwang, SJ., Atkinson, EJ., Lohman, K., Cornelis, MC., Tönjes, A., Chouraki, V., Holliday, EG., Sorice, R., Kutalik, Z., Deshmukh, H., Ulivi, S., Chu, AY., Murgia, F., Trompet, S., Imboden, M., Kollerits, B., Pistis, G., Harris, TB., Launer, LJ., Aspelund, T., Eiriksdottir, G., Mitchell, BD., Schmidt, H., Cavalieri, M., Rao, M., Hu, FB., Demirkan, A., Oostra, BA., de Andrade, M., Turner, ST., Ding, J., Andrews, JS., Freedman, BI., Döring, A., Wichmann, HE., Kolcic, I., Zemunik, T., Boban, M., Minelli, C., Wheeler, HE., Igl, W., Zaboli, G., Wild, SH., Wright, AF., Campbell, H., Ellinghaus, D., Nöthlings, U., Jacobs, G., Biffar, R., Endlich, K., Ernst, F., Homuth, G., Kroemer, HK., Nauck, M., Stracke, S., Völker, U., Völzke, H., Kovacs, P., Stumvoll, M., Mägi, R., Hofman, A., Uitterlinden, AG., Rivadeneira, F., Aulchenko, YS., Polasek, O., Hastie, N., Vitart, V., Helmer, C., Wang, JJ., Ruggiero, D., Bergmann, S., Viikari, J., Nikopensius, T., Province, M., Ketkar, S., Colhoun, H., Doney, A., Robino, A., Giulianini, F., Krämer, BK., Portas, L., Ford, I., Buckley, BM., Adam, M., Thun, GA., Paulweber, B., Haun, M., Sala, C., Metzger, M., Mitchell, P., Ciullo, M., Kim, SK., Vollenweider, P., Raitakari, O., Palmer, C., Gasparini, P., Pirastu, M., Jukema, J., Probst-Hensch, NM., Kronenberg, F., Toniolo, D., Shuldiner, AR., Coresh, J., Schmidt, R., Ferrucci, L., Siscovick, DS., van Duijn CM., Borecki, I., Kardia, SL., Liu, Y., Curhan, GC., Rudan, I., Gyllensten, U., Wilson, JF., Franke, A., Pramstaller, PP., Rettig, R., Prokopenko, I., Witteman, JC., Hayward, C., Ridker, P., Parsa, A., Bochud, M., Heid, IM., Goessling, W., Chasman, DI., Kao, W., Fox, CS., de Boer IH., Glazer, NL., Peralta, CA., Kutalik£££Zoltán£££ Z., Luan£££Jian'an£££ J., Zhao, JH., Akylbekova, E., Kramer, H., van der Harst, P., Arking, DE., Franceschini, N., Egan, J., Hernandez, D., Reilly, M., Townsend, RR., Lumley, T., Psaty, BM., Kestenbaum, B., Haritunians, T., Waeber, G., Mooser, V., Waterworth, D., Florez, JC., Meigs, JB., Lu, X., Leak, TS., Aasarød, K., Skorpen, F., Baumert, J., Devuyst, O., Mychaleckyj, JC., Bakker, SJ., Kedenko, L., Coassin, S., Hastie, ND., Curhan, G., Ärnlöv, J., Hallan, S., Navis, G., Shlipak, MG., Bull, SB., Paterson, AD., Wareham, NJ., Loos, RJ., Rotter, JI., Cupples, L., Beckmann, JS., Dreisbach, AW., Kao, WH., Anderson, CA., Gordon, SD., Guo, Q., Henders, A., Lambert, A., Lee, SH., Kraft, P., Kennedy, SH., Macgregor, S., Martin, NG., Missmer, SA., Montgomery, GW., Morris, AP., Nyholt, DR., Painter, JN., Roseman, F., Treloar, SA., Visscher, PM., Wallace, L., Zondervan, KT., Sandholm, N., Salem, RM., McKnight, AJ., Brennan, EP., Forsblom, C., Isakova, T., McKay, GJ., Williams, WW., Sadlier, DM., Mäkinen, VP., Swan, EJ., Boright, AP., Ahlqvist, E., Keller, BJ., Huang, H., Ahola, A., Fagerholm, E., Gordin, D., Harjutsalo, V., He, B., Heikkilä, O., Hietala, K., Kytö, J., Lahermo£££Päivi£££ P., Lehto, M., Österholm, AM., Parkkonen, M., Pitkäniemi, J., Rosengård-Bärlund, M., Saraheimo, M., Sarti, C., Söderlund, J., Soro-Paavonen, A., Syreeni, A., Thorn, LM., Tikkanen, H., Tolonen, N., Tryggvason, K., Tuomilehto, J., Wadén, J., Gill, GV., Prior, S., Guiducci, C., Mirel, DB., Taylor, A., Hosseini, M., Parving, HH., Rossing, P., Tarnow, L., Ladenvall, C., Alhenc-Gelas, F., Lefebvre, P., Rigalleau, V., Roussel, R., Tregouet, DA., Maestroni, A., Maestroni, S., Falhammar, H., Gu, T., Möllsten, A., Cimponeriu, D., Mihai, I., Mota, M., Mota, E., Serafinceanu, C., Stavarachi, M., Hanson, RL., Nelson, RG., Kretzler, M., Colhoun, HM., Panduru, NM., Gu, HF., Brismar, K., Zerbini, G., Hadjadj, S., Marre, M., Lajer, M., Waggott, D., Savage, DA., Bain, SC., Martin, F., Hirschhorn, JN., Godson, C., Groop, PH., Maxwell, AP., Schmidt, EM., Sengupta, S., Peloso, GM., Ganna, A., Chen, J., Buchkovich, ML., Mora, S., Bragg-Gresham, JL., Chang, HY., Demirkan£££Ayşe£££ A., Den Hertog HM., Donnelly, LA., Ehret, GB., Feitosa, MF., Ferreira, T., Fraser, RM., Freitag, DF., Gurdasani, D., Heikkilä, K., Hyppönen, E., Jackson, AU., Johnson, T., Kaakinen, M., Kettunen, J., Li, X., Magnusson, PK., Mangino, M., Montasser, ME., Nolte, IM., Palmer, CD., Petersen, AK., Sanna, S., Saxena, R., Service, SK., Shah, S., Sidore, C., Surakka, I., Teslovich, TM., Van den Herik EG., Volcik, KA., Wong, A., Wu, Y., Asiki, G., Been, LF., Bolton, JL., Bonnycastle, LL., Burnett, MS., Cesana, G., Doring, A., Elliott, P., Eyjolfsson, GI., Goodarzi, MO., Grallert, H., Gravito, ML., Groves, CJ., Hartikainen, AL., Hicks, AA., Hung, YJ., Jones, MR., Kaleebu, P., Kastelein, JJ., Khaw, KT., Kim, E., Komulainen, P., Kumari, M., Lehtimaki, T., Lin, SY., Lindstrom, J., Mach, F., McArdle, WL., Muller, G., Nagaraja, R., Narisu, N., Nieminen, TV., Nsubuga, RN., Olafsson, I., Ong, KK., Palotie, A., Papamarkou, T., Pomilla, C., Pouta, A., Ridker, PM., Ruokonen, A., Samani, N., Scharnagl, H., Seeley, J., Silander, K., Stančáková, A., Swift, AJ., Tiret, L., van Pelt, L., Vedantam, S., Wainwright, N., Wijmenga, C., Willemsen, G., Wilsgaard, T., Young, EH., Adair, LS., Bandinelli, S., Bennett, F., Boomsma, DI., Borecki, IB., Bornstein, SR., Bovet, P., Burnier, M., Chakravarti, A., Chen, YD., Collins, FS., Cooper, RS., Feranil, AB., Ferrieres, J., Freimer, NB., Gieger, C., Groop, LC., Hingorani, A., Hovingh, G., Hsiung, CA., Humphries, SE., Hunt, SC., Hveem, K., Jarvelin, MR., Jula, A., Kaprio, J., Kesäniemi, A., Kivimaki, M., Koudstaal, PJ., Krauss, RM., Kuh, D., Kyvik, KO., Lakka, TA., Lindgren, CM., McKenzie, CA., Meneton, P., Moilanen, L., Munroe, PB., Njølstad, I., Power, C., Price, JF., Rauramaa, R., Sanghera, DK., Saramies, J., Schwarz, PE., Sheu, WH., Spector, TD., Strachan, DP., Tayo, BO., Tremoli, E., Uusitupa, M., Whitfield, JB., Wolffenbuttel, BH., Ordovas, JM., Rich, SS., Mohlke, KL., Abecasis, GR., Abecasis, G., Caulfield, M., Chasman, D., Ehret, G., Johnson, A., Johnson, L., Larson, M., Levy, D., Munroe, P., Newton-Cheh, C., O'Reilly, P., Palmas, W., Psaty, B., Rice, K., Smith, A., Snider, H., Tobin, M., Van Duijn, C., Verwoert, G., Rice, KM., Tobin, MD., Verwoert, GC., Pihur, V., O'Reilly, PF., Amin, N., Launer, L., Aulchenko, Y., Heath, S., Sõber, S., Arora, P., Zhang, F., Lucas, G., Milaneschi, Y., Parker, AN., Fava, C., Fox, ER., Go, MJ., Sjögren, M., Vinay, D., Alexander, M., Tabara, Y., Shaw-Hawkins, S., Whincup, PH., Shi, G., Tayo, B., Seielstad, M., Sim, X., Nguyen, KD., Matullo, G., Gaunt, TR., Onland-Moret, NC., Cooper, MN., Platou, CG., Org, E., Hardy, R., Dahgam, S., Palmen, J., Kuznetsova, T., Uiterwaal, CS., Adeyemo, A., Ludwig, B., Tomaszewski, M., Tzoulaki, I., Palmer, ND., Garcia, M., Chang, YP., Steinle, NI., Grobbee, DE., Morrison, AC., Najjar, S., Hadley, D., Brown, MJ., Connell, JM., Hingorani, AD., Day, IN., Lawlor, DA., Beilby, JP., Lawrence, RW., Ongen, H., Li, Y., Young, JH., Bis, JC., Lee, NR., Bolton, JA., Chaturvedi, N., Frayling, TM., Islam, M., Jafar, TH., Kulkarni, SR., Grässler, J., Howard, P., Guarrera, S., Ricceri, F., Emilsson, V., Plump, A., Weder, AB., Sun, YV., Bergman, RN., Scott, LJ., Stringham, HM., Peltonen, L., Vartiainen, E., Brand, SM., Staessen, JA., Wang, TJ., Burton, PR., Artigas, MS., Dong, Y., Snieder, H., Wang, X., Zhu, H., Lohman, KK., Rudock, ME., Heckbert, SR., Smith, NL., Wiggins, KL., Doumatey, A., Shriner, D., Veldre, G., Viigimaa, M., Kinra, S., Prabhakaran, D., Tripathy, V., Langefeld, CD., Rosengren, A., Thelle, DS., Corsi, AM., Singleton, A., Forrester, T., Hilton, G., Salako, T., Iwai, N., Kita, Y., Ogihara, T., Ohkubo, T., Okamura, T., Ueshima, H., Umemura, S., Eyheramendy, S., Meitinger, T., Cho, YS., Kim, HL., Scott, J., Sehmi, JS., Hedblad, B., Nilsson, P., Smith, GD., Raffel, LJ., Yao, J., Schwartz, SM., Ikram, M., Longstreth W.<Suffix>Jr</Suffix>, Mosley, TH., Seshadri, S., Shrine, NR., Wain, LV., Morken, MA., Laitinen, J., Zitting, P., Cooper, JA., van Gilst WH., Janipalli, CS., Mani, K., Yajnik, CS., Mattace-Raso, FU., Lakatta, EG., Orru, M., Scuteri, A., Ala-Korpela, M., Kangas, AJ., Soininen, P., Tukiainen, T., Würtz, P., Ong, RT., Dörr, M., Galan, P., Hercberg, S., Lathrop, M., Zelenika, D., Zhai, G., Meschia, JF., Nalls, MA., Sharma, P., Terzic, J., Kumar, M., Denniff, M., Zukowska-Szczechowska, E., Wagenknecht, LE., Fowkes, F., Charchar, FJ., Guo, X., Rotimi, C., Bots, ML., Brand, E., Talmud, PJ., Nyberg, F., Laan, M., Palmer, LJ., van der Schouw YT., Casas, JP., Vineis, P., Ganesh, SK., Wong, TY., Tai, ES., Rao, DC., Morris, RW., Dominiczak, AF., Marmot, MG., Miki, T., Chandak, GR., Zhu, X., Gyllensten, UB., Elosua, R., Soranzo, N., Sijbrands, EJ., Uda, M., Vasan, RS., Larson, MG., Järvelin, MR., Caulfield, MJ., Alizadeh, BZ., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., Hillege, HL., van der Klauw MM., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Stolk, RP., Scott, RA., Lagou, V., Welch, RP., Wheeler, E., Rehnberg, E., Rasmussen-Torvik, LJ., Yengo£££Loïc£££ L., Lecoeur, C., Johnson, PC., Jukema, JW., Mahajan, A., Verweij, N., Hottenga, JJ., Sennblad, B., Salo, P., Timpson, NJ., Evans, DM., St Pourcain, B., Hui, J., Bielak, LF., Zhao, W., Horikoshi, M., Navarro, P., Esko, T., Fall, T., Raychaudhuri, S., Chen, H., Robertson, N., Rybin, D., Willems, SM., Chines, PS., Song, K., An, P., Marullo, L., Jansen, H., Oldehinkel, AJ., Pankow, JS., North, KE., Forouhi, NG., Edkins, S., Varga, TV., Oksa, H., Antonella, M., Kong, A., Herder, C., Antti, J., Small, K., Miljkovic, I., Atalay, M., Kiess, W., James, AL., Smit, JH., Campbell, S., Fowkes, GR., Lindström, J., Basart, HV., Rathmann, W., Maerz, W., Province, MA., Watanabe, RM., de Geus EJ., Penninx, BW., Dedoussis, GV., Toenjes, A., Peyser, PA., Körner, A., Lakka, T., Keinanen-Kiukaanniemi, SM., Saaristo, TE., Dupuis, J., Sattar, N., Cucca, F., Balkau, B., Froguel, P., Bouatia-Naji, N., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., O'Donnell, CJ., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Subirana, I., Sala, J., Ramos, R., Williams, G., Nathan, DM., MacRae, CA., Berglund, G., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Wright, BJ., Ball, SG., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Fischer, M., Grosshennig, A., Preuss, M., Ouwehand, W., Scholz, M., Goodall, A., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., Hólm, H., Xie, C., Siscovick, D., Ahmadi, KR., Ainali, C., Barrett, A., Bataille, V., Bell, JT., Buil, A., Dermitzakis, ET., Dimas, AS., Durbin, R., Glass, D., Hassanali, N., Hedman£££Åsa K£££ ÅK., Ingle, C., Keildson, S., Knowles, D., Krestyaninova, M., Lowe, CE., Meduri, E., di Meglio, P., Min, JL., Montgomery, SB., Nestle, FO., Nica, AC., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, SY., Small, KS., Surdulescu, G., Travers, ME., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, TP., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., Heiss, G., Taylor, K., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Crawford, D., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Ritchie, M., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Carlson, C., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., Perry, JR., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, WV., Albrecht, E., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Eriksson, JG., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Karasik, D., Keyzer, J., Kiel, DP., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Styrkarsdottir, U., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Yerges-Armstrong, LM., Zgaga, L., Zillikens, MC., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Streeten, EA., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Koller, DL., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Eriksson, J., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Peacock, M., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., van Meurs JB., Weedon, MN., Wichmann, H., Young, L., Bierut, LJ., Boyd, HA., Econs, MJ., Van T'Hooft, Ferdinand M., Njølstad, Inger, Abecasis, Gonçalo R., Barroso, Inɥ, The MIGEN Consortium, Investigator, Casari, GIORGIO NEVIO, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Clinical Haematology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Locke, A, Kahali, B, Berndt, S, Justice, A, Pers, T, Day, F, Powell, C, Vedantam, S, Buchkovich, M, Yang, J, Croteau-Chonka, D, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, J, Magi, R, Randall, J, Winkler, T, Wood, A, Workalemahu, T, Faul, J, Smith, J, Zhao, J, Zhao, W, Chen, J, Fehrmann, R, Hedman, A, Karjalainen, J, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bolton, J, Bragg-Gresham, J, Buyske, S, Demirkan, A, Deng, G, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Goel, A, Gong, J, Jackson, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Leach, I, Medina-Gomez, C, Medland, S, Nalls, M, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Shungin, D, Stancakova, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet-Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Isaacs, A, Albrecht, E, Arnlov, J, Arscott, G, Attwood, A, Bandinelli, S, Barrett, A, Bas, I, Bellis, C, Bennett, A, Berne, C, Blagieva, R, Bluher, M, Bohringer, S, Bonnycastle, L, Bottcher, Y, Boyd, H, Bruinenberg, M, Caspersen, I, Chen, Y, Clarke, R, Daw, E, de Craen, A, Delgado, G, Dimitriou, M, Doney, A, Eklund, N, Estrada, K, Eury, E, Folkersen, L, Fraser, R, Garcia, M, Geller, F, Giedraitis, V, Gigante, B, Go, A, Golay, A, Goodall, A, Gordon, S, Gorski, M, Grabe, H, Grallert, H, Grammer, T, Grassler, J, Gronberg, H, Groves, C, Gusto, G, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heard-Costa, N, Helmer, Q, Hengstenberg, C, Holmen, O, Hottenga, J, James, A, Jeff, J, Johansson, A, Jolley, J, Juliusdottir, T, Kinnunen, L, Koenig, W, Koskenvuo, M, Kratzer, W, Laitinen, J, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindstrom, J, Lo, K, Lobbens, S, Lorbeer, R, Lu, Y, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Mclachlan, S, Menni, C, Merger, S, Mihailov, E, Milani, L, Moayyeri, A, Monda, K, Morken, M, Mulas, A, Muller, G, Muller-Nurasyid, M, Musk, A, Nagaraja, R, Nothen, M, Nolte, I, Pilz, S, Rayner, N, Renstrom, F, Rettig, R, Ried, J, Ripke, S, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Scott, W, Seufferlein, T, Shi, J, Smith, A, Smolonska, J, Stanton, A, Steinthorsdottir, V, Stirrups, K, Stringham, H, Sundstrom, J, Swertz, M, Swift, A, Syvanen, A, Tan, S, Tayo, B, Thorand, B, Thorleifsson, G, Tyrer, J, Uh, H, Vandenput, L, Verhulst, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Warren, H, Waterworth, D, Weedon, M, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Brennan, E, Choi, M, Dastani, Z, Drong, A, Eriksson, P, Franco-Cereceda, A, Gadin, J, Gharavi, A, Goddard, M, Handsaker, R, Huang, J, Karpe, F, Kathiresan, S, Keildson, S, Kiryluk, K, Kubo, M, Lee, J, Liang, L, Lifton, R, Ma, B, Mccarroll, S, Mcknight, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Okada, Y, Perry, J, Dorajoo, R, Reinmaa, E, Salem, R, Sandholm, N, Scott, R, Stolk, L, Takahashi, A, Van't Hooft, F, Vinkhuyzen, A, Westra, H, Zheng, W, Zondervan, K, Heath, A, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Bovet, P, Campbell, H, Caulfield, M, Cesana, G, Chakravarti, A, Chasman, D, Chines, P, Collins, F, Crawford, D, Cupples, L, Cusi, D, Danesh, J, de Faire, U, Den Ruijter, H, Dominiczak, A, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Felix, S, Ferrannini, E, Ferrieres, J, Ford, I, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gejman, P, Gieger, C, Gottesman, O, Gudnason, V, Gyllensten, U, Hall, A, Harris, T, Hattersley, A, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Homuth, G, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Illig, T, Jacobs, K, Jarvelin, M, Jockel, K, Johansen, B, Jousilahti, P, Jukema, J, Jula, A, Kaprio, J, Kastelein, J, Keinanen-Kiukaanniemi, S, Kiemeney, L, Knekt, P, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Marchand, L, Lehtimaki, T, Lyssenko, V, Mannisto, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Moll, F, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Madden, P, Pasterkamp, G, Peden, J, Peters, A, Postma, D, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Rioux, J, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schunkert, H, Schwarz, P, Sever, P, Shuldiner, A, Sinisalo, J, Stolk, R, Strauch, K, Tonjes, A, Tregouet, D, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Volker, U, Waeber, G, Willemsen, G, Witteman, J, Zillikens, M, Adair, L, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bornstein, S, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hui, J, Hunter, D, Hveem, K, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, Marz, W, Melbye, M, Metspalu, A, Moebus, S, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Perusse, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sattar, N, Schadt, E, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Walker, M, Wallaschofski, H, Wareham, N, Watkins, H, Weir, D, Wichmann, H, Wilson, J, Zanen, P, Borecki, I, Deloukas, P, Fox, C, Heid, I, O'Connell, J, Strachan, D, Stefansson, K, van Duijn, C, Abecasis, G, Franke, L, Frayling, T, Mccarthy, M, Visscher, P, Scherag, A, Willer, C, Boehnke, M, Mohlke, K, Lindgren, C, Beckmann, J, Barroso, I, North, K, Ingelsson, E, Hirschhorn, J, Loos, R, Speliotes, E, Thompson, J, Goldstein, B, Konig, I, Cazier, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikainen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Claudi-Boehm, S, Cox, D, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schafer, A, Sivananthan, M, Song, C, Stewart, A, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Tsun-Po, Y, Basart, H, Brambilla, P, Cambien, F, Cupples, A, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kahonen, M, Kee, F, Kim, H, Klopp, N, Kuulasmaa, K, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Wallentin, L, Zimmermann, M, Nieminen, M, Sandhu, M, Pastinen, T, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Roberts, R, Pattaro, C, Kottgen, A, Garnaas, M, Boger, C, Fuchsberger, C, Olden, M, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Liu, C, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Lohman, K, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, Hu, F, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Doring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Ellinghaus, D, Nothlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Volzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Kramer, B, Portas, L, Buckley, B, Adam, M, Thun, G, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Vollenweider, P, Gasparini, P, Pirastu, M, Probst-Hensch, N, Kronenberg, F, Toniolo, D, Coresh, J, Schmidt, R, Siscovick, D, Kardia, S, Curhan, G, Franke, A, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, Arking, D, Franceschini, N, Egan, J, Hernandez, D, Townsend, R, Lumley, T, Psaty, B, Kestenbaum, B, Haritunians, T, Mooser, V, Florez, J, Meigs, J, Lu, X, Leak, T, Aasarod, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Kedenko, L, Coassin, S, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Dreisbach, A, Anderson, C, Guo, Q, Henders, A, Lambert, A, Lee, S, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Makinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkila, O, Hietala, K, Kyto, J, Lahermo, P, Lehto, M, Osterholm, A, Parkkonen, M, Pitkaniemi, J, Rosengard-Barlund, M, Saraheimo, M, Sarti, C, Soderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Waden, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc-Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Mollsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Freitag, D, Gurdasani, D, Heikkila, K, Johnson, T, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Teslovich, T, Van den Herik, E, Volcik, K, Wu, Y, Asiki, G, Been, L, Burnett, M, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Khaw, K, Kim, E, Komulainen, P, Lin, S, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Young, E, Bennett, F, Boomsma, D, Burnier, M, Feranil, A, Freimer, N, Hsiung, C, Kesaniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Meneton, P, Moilanen, L, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton-Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sober, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjogren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland-Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Brown, M, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Staessen, J, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace-Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Wurtz, P, Ong, R, Dorr, M, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, Ormel, J, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Rasmussen-Torvik, L, Lecoeur, C, Johnson, P, Sennblad, B, Salo, P, Timpson, N, Evans, D, St Pourcain, B, Bielak, L, Horikoshi, M, Navarro, P, Raychaudhuri, S, Chen, H, Rybin, D, Willems, S, Song, K, An, P, Marullo, L, Jansen, H, Pankow, J, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Small, K, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Penninx, B, Toenjes, A, Peyser, P, Korner, A, Dupuis, J, Cucca, F, Balkau, B, Bouatia-Naji, N, Purcell, S, Musunuru, K, Ardissino, D, Mannucci, P, Anand, S, Engert, J, Morgan, T, Spertus, J, Stoll, M, Girelli, D, Mckeown, P, Patterson, C, Merlini, P, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Subirana, I, Sala, J, Ramos, R, Williams, G, Nathan, D, Macrae, C, Berglund, G, Asselta, R, Duga, S, Spreafico, M, Daly, M, Nemesh, J, Korn, J, Surti, A, Gianniny, L, Parkin, M, Burtt, N, Gabriel, S, Wright, B, Ball, S, Schunkert, I, Linsel-Nitschke, P, Lieb, W, Fischer, M, Grosshennig, A, Preuss, M, Scholz, M, Chen, Z, Wilensky, R, Matthai, W, Qasim, A, Hakonarson, H, Devaney, J, Pichard, A, Kent, K, Satler, L, Lindsay, J, Waksman, R, Knouff, C, Scheffold, T, Berger, K, Huge, A, Martinelli, N, Olivieri, O, Corrocher, R, Xie, C, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, Di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Yang, T, Higashio, J, Williams, R, Nato, A, Ambite, J, Deelman, E, Manolio, T, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown-Gentry, K, Thornton-Wells, T, Dumitrescu, L, Bush, W, Mitchell, S, Goodloe, R, Wilson, S, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Spencer, K, Pendergrass, S, Le Marchand, L, Park, L, Tiirikainen, M, Kolonel, L, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Anderson, G, Carlson, C, Prentice, R, Lacroix, A, Wu, C, Carty, C, Rosse, S, Young, A, Kocarnik, J, Lin, Y, Jackson, R, Duggan, D, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hankinson, S, Hass, M, Janssens, A, Karasik, D, Keyzer, J, Kiel, D, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Streeten, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Koller, D, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Couper, D, Easton, D, Foroud, T, Kilpelainen, T, Li, S, Murray, S, Ness, A, Northstone, K, Peacock, M, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segre, A, Sovio, U, Srinivasan, S, Tammesoo, M, van Meurs, J, Young, L, Bierut, L, Econs, M, The ADIPOGen Consortium, The AGEN-BMI Working Group, The CARDIOGRAMplusC4D Consortium, The CKDGen Consortium, The GLGC, The ICBP, The MAGIC Investigators, The MuTHER Consortium, The MIGen Consortium, The PAGE Consortium, The ReproGen Consortium, The GENIE Consortium, The International Endogene Consortium, Berndt, Sonja I, Justice, Anne E, Hyppönen, Elina Tuulikki, Epidemiology and Data Science, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Male, LOCI, Genome-wide association study, Continental Population Groups/genetics, VARIANTS, Body Mass Index, Insulin Secretion, Insulin, Age Factor, Adiposity, ddc:616, Adipogenesis, Genetic Predisposition to Disease/genetics, Synapse, 3. Good health, Continental Population Group, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], GENOME-WIDE ASSOCIATIONPROVIDES INSIGHTSGLYCEMIC TRAITSLOCIMETAANALYSISVARIANTSINDIVIDUALSHIPPOCAMPALARCHITECTURETOPIRAMATE, ddc:500, Adipogenesis/genetics, Single Nucleotide/genetics, Age Factors, Continental Population Groups, Energy Metabolism, Europe, Female, Genetic Predisposition to Disease, Glutamic Acid, Humans, Obesity, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Synapses, Genome-Wide Association Study, Multidisciplinary, genetics [Adiposity], Human, Socio-culturale, genetics [Energy Metabolism], ta3111, genetic, body mass index, obesity, SDG 3 - Good Health and Well-being, GLYCEMIC TRAITS, genetics [Continental Population Groups], Genetic variability, Polymorphism, GENOME-WIDE ASSOCIATION, genetics [Adipogenesis], METAANALYSIS, Genetic association, Adipogenesi, genetics [Quantitative Trait Loci], ta1184, metabolism [Glutamic Acid], ta1182, PATHWAYS, metabolism [Synapses], ta3121, medicine.disease, metabolism [Insulin], Adiposity/genetics, Clinical Medicine, Quantitative Trait Loci/genetics, Body mass index, HUMAN HEIGHT, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Synapses/metabolism, Medizin, Obesity/genetics, Bioinformatics, genetic basis, Obesity/metabolism, genetics [Obesity], body mass index (BMI), genetics [Genetic Predisposition to Disease], ethnology [Europe], 2. Zero hunger, Genetics, ARCHITECTURE, Genetics of obesity, Medicine (all), Single Nucleotide, Polymorphism, Single Nucleotide/genetics, Insulin/metabolism/secretion, Glutamic Acid/metabolism, genetics [Polymorphism, Single Nucleotide], EXPRESSION, Insulin/metabolism, PROVIDES INSIGHTS, genetics [Racial Groups], Biology, Obesity/genetics/metabolism, Europe/ethnology, metabolism [Obesity], Mendelian randomization, medicine, Energy Metabolism/genetics, body mass, genetic analysis, obesity, Klinisk medicin
Abstract: Item does not contain fulltext Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for approximately 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Published: 2015

33. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Author: Laura J. Scott, Bernie Devlin, Steven A. McCarroll, James S. Sutcliffe, Stefan Herms, Yunjung Kim, Richard O. Day, Thomas F. Wienker, Frank Dudbridge, I. Nicol Ferrier, Bettina Konte, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Detelina Grozeva, Herbert Roeyers, Peter Holmans, Colm O'Dushlaine, Scott D. Gordon, Sarah E. Bergen, Fan Meng, Morten Mattingsdal, Hugh Gurling, Ina Giegling, Gerard van Grootheest, Ania Korszun, Markus J. Schwarz, George Kirov, Sebastian Zöllner, Kenneth S. Kendler, Nicholas G. Martin, Michael Conlon O'Donovan, Michael C. Neale, Jim van Os, Aravinda Chakravarti, Timothy W. Yu, Mikael Landén, Inez Myin-Germeys, Markus M. Nöthen, Kathryn Roeder, James B. Potash, Alan W. McLean, Louise Gallagher, Anna K. Kähler, Thomas Bettecken, Nigel Williams, Frank Bellivier, Joseph D. Buxbaum, Derek W. Morris, Susan L. Smalley, Jung-Ying Tzeng, Martin Schalling, Douglas M. Ruderfer, Caroline M. Nievergelt, T. Scott Stroup, David H. Ledbetter, Jennifer Crosbie, Anita Thapar, Barbara Franke, Jeffrey A. Lieberman, Huda Akil, Miguel Casas, Daniel H. Geschwind, Paul Cormican, Bertram Müller-Myhsok, Lyudmila Georgieva, Robert Krasucki, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Gerard D. Schellenberg, Todd Lencz, Melvin G. McInnis, Catalina Betancur, Josep Antoni Ramos-Quiroga, Stephen Sanders, Eftichia Duketis, Don H. Linszen, Matthew W. State, Richard M. Myers, Soumya Raychaudhuri, Lizzy Rossin, Howard J. Edenberg, Michael E. Goddard, S. Hong Lee, Elisabeth B. Binder, Pablo V. Gejman, William A. Scheftner, Wolfgang Maier, Judith A. Badner, Christel M. Middeldorp, Maria Helena Pinto de Azevedo, Johannes H. Smit, Willem A. Nolen, Lieuwe de Haan, Gonneke Willemsen, Keith Matthews, Ellen M. Wijsman, Jennifer K. Lowe, Rebecca McKinney, Magdalena Gross, Dorothy E. Grice, James A. Knowles, Andrew C. Heath, Jana Strohmaier, Vishwajit L. Nimgaonkar, William Byerley, William E. Bunney, Dan E. Arking, Andrew McQuillin, William M. McMahon, Manuel Mattheisen, Hans-Christoph Steinhausen, Joseph Biederman, Guy A. Rouleau, James J. McGough, Sian Caesar, Edward M. Scolnick, Lefkos T. Middleton, Jack D. Barchas, Ian B. Hickie, Danyu Lin, Patrik K. E. Magnusson, Douglas Blackwood, Francis J. McMahon, Ingrid Agartz, Elena Maestrini, Marian L. Hamshere, Lindsey Kent, Walter J. Muir, Stephan Ripke, Lydia Krabbendam, Christine Fraser, Maria Hipolito, Louise Frisén, Eric Fombonne, Emma M. Quinn, Michael Bauer, Richard P. Ebstein, Michael Steffens, Jordan W. Smoller, Stanley J. Watson, Michael Boehnke, Philip Asherson, Agatino Battaglia, Elliot S. Gershon, Russell Schachar, Marcus Ising, Peng Zhang, Margaret A. Pericak-Vance, Joachim Hallmayer, Sean Ennis, Radhika Kandaswamy, René S. Kahn, Susanne Hoefels, Thomas W. Mühleisen, Pamela Sklar, Paul Lichtenstein, Verneri Anttila, Michael L. Cuccaro, Florian Holsboer, René Breuer, Eric M. Morrow, Vinay Puri, Naomi R. Wray, Szabocls Szelinger, Sabine M. Klauck, John B. Vincent, Shrikant Mane, Aribert Rothenberger, Marion Friedl, Ian Jones, Khalid Choudhury, Michael R. Barnes, Adebayo Anjorin, Edwin H. Cook, William Lawson, Allan H. Young, Lambertus Klei, Bryan J. Mowry, Johannes Schumacher, Michael Gill, James L. Kennedy, Marcella Rietschel, Aiden Corvin, Henrik B. Rasmussen, Susmita Datta, Kimberly Chambert, Daniel Moreno-De-Luca, Benjamin S. Pickard, Stan F. Nelson, Veronica J. Vieland, Stephen W. Scherer, Peter M. Visscher, John Strauss, Andreas Reif, Andrew D. Paterson, Ann Olincy, Phoenix Kwan, Anthony J. Bailey, Patrick F. Sullivan, Pierandrea Muglia, Gunnar Morken, Susanne Lucae, Ayman H. Fanous, Jacob Lawrence, Donald J. MacIntyre, Nancy G. Buccola, Rita M. Cantor, Christina M. Hultman, Weihua Guan, Anthony P. Monaco, Jouke-Jan Hottenga, Elaine Kenny, Jianxin Shi, Dale R. Nyholt, Kevin A. McGhee, Falk W. Lohoff, Jonna Kuntsi, Niklas Långström, John I. Nurnberger, Nelson B. Freimer, Erin N. Smith, John P. Rice, Michael T. Murtha, Thomas H. Wassink, Alexandre A. Todorov, Edmund J.S. Sonuga-Barke, Dan Rujescu, Roy H. Perlis, John S. Witte, Christopher A. Walsh, Matthew C. Keller, Pamela B. Mahon, Patrick J. McGrath, Susan L. Santangelo, Annette M. Hartmann, Ole A. Andreassen, Tatiana Foroud, Shaun Purcell, Josef Frank, Douglas F. Levinson, William Coryell, Ana Miranda, Alan F. Schatzberg, Peter Szatmari, Jun Li, Gerome Breen, Stephen V. Faraone, Anil K. Malhotra, Helena Medeiros, Martin A. Kohli, Nicholas Bass, Catherine Lord, Peter Propping, Wei Xu, Federica Tozzi, Ivan Nikolov, Jan K. Buitelaar, Thomas G. Schulze, Katherine Gordon-Smith, Michele L. Pergadia, Fritz Poustka, Valentina Moskvina, David Curtis, Tobias Banaschewski, Devin Absher, Danielle Posthuma, Stanley Zammit, Gary Donohoe, Ingrid Melle, Karola Rehnström, Thomas Hansen, Myrna M. Weissman, Stanley I. Shyn, Hakon Hakonarson, Christa Lese Martin, Digby Quested, Darina Czamara, Jeremy R. Parr, Pamela A. F. Madden, Jens Treutlein, Aarno Palotie, Robert Freedman, Sandra Meier, Bru Cormand, Nicholas J. Schork, Michele T. Pato, John R. Kelsoe, Vanessa Hus, Frans G. Zitman, Josephine Elia, David St Clair, Roel A. Ophoff, Peter McGuffin, Jonathan Pimm, Jonathan L. Haines, Wiepke Cahn, Matthew Flickinger, Steven P. Hamilton, Michael John Owen, Paul D. Shilling, Jeremy M. Silverman, David Craig, Mark J. Daly, Sarah E. Medland, Robert D. Oades, Marion Leboyer, Alan R. Sanders, Vihra Milanova, Chunyu Liu, Jobst Meyer, Dorret I. Boomsma, Evaristus A. Nwulia, Thomas B. Barrett, Jennifer L. Moran, Donald W. Black, Mònica Bayés, Witte J.G. Hoogendijk, Franziska Degenhardt, Benjamin M. Neale, Daniel L. Koller, Carlos N. Pato, Nicholas John Craddock, Richard Bruggeman, Enda M. Byrne, Edward G. Jones, Eco J. C. de Geus, Stéphane Jamain, Jubao Duan, Anne Farmer, Astrid M. Vicente, Grant W. Montgomery, Thomas Werge, Cathryn M. Lewis, Srdjan Djurovic, Phil Lee, Richard Anney, Elaine K. Green, Wade H. Berrettini, Peter P. Zandi, Susan L. Slager, Stephanie H. Witt, Ian W. Craig, Lisa Jones, Sven Cichon, Bruno Etain, Mark Lathrop, Hilary Coon, Robert C. Thompson, Lena Backlund, A. Jeremy Willsey, Andres Ingason, Christine M. Freitag, Sandra K. Loo, Guiomar Oliveira, Line Olsen, Edwin J. C. G. van den Oord, Geraldine Dawson, Joseph A. Sergeant, David A. Collier, Farooq Amin, Srinivasa Thirumalai, Manfred Uhr, Joseph Piven, Andrew M. McIntosh, Anjali K. Henders, Urban Ösby, Klaus-Peter Lesch, Tiffany A. Greenwood, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Lee, S Hong, Ripke, Stephan, Neale, Benjamin M, Faraone, Stephen V, Wray, Naomi R, Cross-Disorder Group of the Psychiatric Genomics Consortium, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Queensland Brain Institute, University of Queensland [Brisbane], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], SUNY Upstate Medical University, State University of New York (SUNY), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Psychiatric and Neurodevelopmental Genetics Unit, Queensland Centre for Mental Health Research, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council (MRC)-School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], New South Wales Department of Primary Industries (NSW DPI), Faculty of Land and Food Resources, University of Melbourne, HudsonAlpha Institute for Biotechnology [Huntsville, AL], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Diakonhjemmet Hospital, University of Michigan [Ann Arbor], University of Michigan System, Molecular and Behavioral Neuroscience Institute (MBNI), University of Michigan System-University of Michigan System, Emory University [Atlanta, GA], Oslo University Hospital [Oslo], University College of London [London] (UCL), Trinity College Dublin, Johns Hopkins University School of Medicine [Baltimore], MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, King's College London, University of Coimbra [Portugal] (UC), Karolinska Institutet [Stockholm], University of Chicago, University of British Columbia (UBC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Weill Medical College of Cornell University [New York], GlaxoSmithKline, Glaxo Smith Kline, Portland Veterans Administration Medical Center, Windeyer Institute for Medical Sciences, IRCCS Fondazione Stella Maris [Pisa], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Department of Psychiatry [Philadelphia], University of Pennsylvania, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Massachusetts General Hospital [Boston, MA, USA], University of Iowa [Iowa City], University of Edinburgh, Royal Hospital for Sick Children [Edinburgh], The Scripps Research Institute [La Jolla, San Diego], MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Institute of Medical Sciences, University of Aberdeen, Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, Department of Psychiatry, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Trinity College Dublin-St. James's Hospital, School of Nursing, Louisiana State University (LSU), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Department of Psychiatry and Human Behavior, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Department of Neuroscience, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Friedman Brain Institute, The Mindich Child Health and Development Institute, University of California [San Francisco] (UC San Francisco), Department of Psychiatry, School of Clinical and Experimental Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Stanley Center for Psychiatric Research, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Mental Health Sciences Unit, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Academic Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Developmental Neuroscience, Neuropsychiatric Genetics Research Group, University of California [San Diego] (UC San Diego), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], East London NHS Foundation Trust, Queen Mary University of London (QMUL), Max-Planck-Institut für Psychiatrie, Genetics Institute, Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Medstar Research Institute, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry and Behavioral Sciences, University of Chicago-NorthShore University Health System, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Psychology Department, National University of Singapore (NUS), Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University (VCU), University of Dundee School of Medicine, University of Dundee, Department of Biostatistics and Center for Statistical Genetics, University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), Howard University College of Medicine, University of Colorado [Denver], Center for Neurobehavioral Genetics, Department of Genomics, Department of Molecular Medicine, Department of Neurology, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Medical Research Council-Cardiff University, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Institute for Human Genetics, Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Clinical and Developmental Psychology, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Clinical Research Unit, Brain & Mind Research Institute-The University of Sydney, Functional Genomics, Neuronal Plasticity / Mouse Behaviour, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Medical Epidemiology and Biostatistics (MEB), Autism and Communicative Disorders Centre, Center for Human Genetic Research, Center for neuroscience-University of California [Davis] (UC Davis), Bioinformatics Research Center, North Carolina State University [Raleigh] (NC State), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Emory University [Atlanta, GA]-Atlanta Veterans Affairs Medical Center, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Medicine, University of St Andrews [Scotland], Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Ecology and Evolutionary Biology, Insitute of Neuroscience and Physiology, University of Gothenburg (GU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Developmental Brain and Behaviour Unit, University of Southampton, Division of Psychiatric Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Statistical Genetics Group, Department of Human Genetics, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry and Psychotherapy, Department of Mental Health, Johns Hopkins University and Hospital, W.M. Keck Biotechnology Resource Laboratory, Yale University [New Haven], Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Genetic Epidemiology Unit, Queensland Institute of Medical Research, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Sorlandet Hospital HF, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Medical Genetics Section, University of Edinburgh-Western General Hospital, Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health [Bethesda] (NIH), Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Division of Mental Health and Addiction, Molecular Psychiatry Laboratory, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Research and Development, First Psychiatric Clinic-Alexander University Hospital, Registo Oncológico Regional-Sul, Instituto Português de Oncologia de Francisco Gentil, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, St. Olav's Hospital, Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Human Genetics Department, University of Pittsburgh (PITT), Institute for Biomedical Imaging and Life Science, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Carolina Institute for Developmental Disabilities, Analytic and Translational Genetics Unit, Rush University Medical Center [Chicago], Julius-Maximilians-Universität Würzburg (JMU), Washington University in Saint Louis (WUSTL), Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Department of Experimental Clinical and Health Psychology, Universiteit Gent = Ghent University (UGENT), Department of Child and Adolescent Psychiatry, Georg-August-University = Georg-August-Universität Göttingen, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Departments of Psychiatry and Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Maine Medical Center, Free University of Amsterdam, Department of Psychiatry and Behavioral Sciences [Stanford], Pathology and Laboratory Medicine, The Scripps Translational Science Institute and The Scripps Research Institute, Psychiatric Center Nordbaden, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), The Scripps Translational Science Institute and Scripps Health, Child and Adolescent Psychiatry, Aarhus University Hospital, Molecular Neuropsychiatry and Development Laboratory, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Translational Genomics Research Institute (TGen), Oxford Health NHS Foundation Trust, Marlborough House Secure Unit, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, University of Toronto, Diamantina Institute, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, University of Washington [Seattle], ArcelorMittal Maizières Research SA, ArcelorMittal, Institute of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, LEARN! - Brain, learning and development, EMGO+ - Mental Health, LEARN!, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, State University of New York (SUNY)-State University of New York (SUNY), Department of Neuroscience and Physiology, Faculty of Land and Environment, Biosciences Research Division, Department of Environment and Primary Industries Victoria, Department of Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), University of California-University of California, Universität Heidelberg [Heidelberg], Cornell University [New York]-Weill Medical College of Cornell University [New York], Bioinformatics, Internal Medicine, Portland Va Medical Center : Ganzini Linda MD, Technische Universität Dresden = Dresden University of Technology (TU Dresden)-University Hospital Carl Gustav Carus, Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona (PCB), University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of California [Irvine] (UCI), University of California-University of California-University of California [Los Angeles] (UCLA), University of Bonn, University of California-University of California-David Geffen School of Medicine [Los Angeles], Cardiff University-Medical Research Council, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Göttingen - Georg-August-Universität Göttingen, Yale University School of Medicine, Georg-August-University [Göttingen], ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayés M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DH, Bloss CS, Boehnke M, Boomsma DI, Breen G, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flickinger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisén L, Gallagher L, Gejman PV, Georgieva L, Gershon ES, Geschwind DH, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP, Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S, Hickie IB, Hipolito M, Hoefels S, Holmans PA, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng JY, Kähler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landén M, Långström N, Lathrop M, Lawrence J, Lawson WB, Leboyer M, Ledbetter DH, Lee PH, Lencz T, Lesch KP, Levinson DF, Lewis CM, Li J, Lichtenstein P, Lieberman JA, Lin DY, Linszen DH, Liu C, Lohoff FW, Loo SK, Lord C, Lowe JK, Lucae S, MacIntyre DJ, Madden PA, Maestrini E, Magnusson PK, Mahon PB, Maier W, Malhotra AK, Mane SM, Martin CL, Martin NG, Mattheisen M, Matthews K, Mattingsdal M, McCarroll SA, McGhee KA, McGough JJ, McGrath PJ, McGuffin P, McInnis MG, McIntosh A, McKinney R, McLean AW, McMahon FJ, McMahon WM, McQuillin A, Medeiros H, Medland SE, Meier S, Melle I, Meng F, Meyer J, Middeldorp CM, Middleton L, Milanova V, Miranda A, Monaco AP, Montgomery GW, Moran JL, Moreno-De-Luca D, Morken G, Morris DW, Morrow EM, Moskvina V, Muglia P, Mühleisen TW, Muir WJ, Müller-Myhsok B, Murtha M, Myers RM, Myin-Germeys I, Neale MC, Nelson SF, Nievergelt CM, Nikolov I, Nimgaonkar V, Nolen WA, Nöthen MM, Nurnberger JI, Nwulia EA, Nyholt DR, O'Dushlaine C, Oades RD, Olincy A, Oliveira G, Olsen L, Ophoff RA, Osby U, Owen MJ, Palotie A, Parr JR, Paterson AD, Pato CN, Pato MT, Penninx BW, Pergadia ML, Pericak-Vance MA, Pickard BS, Pimm J, Piven J, Posthuma D, Potash JB, Poustka F, Propping P, Puri V, Quested DJ, Quinn EM, Ramos-Quiroga JA, Rasmussen HB, Raychaudhuri S, Rehnström K, Reif A, Ribasés M, Rice JP, Rietschel M, Roeder K, Roeyers H, Rossin L, Rothenberger A, Rouleau G, Ruderfer D, Rujescu D, Sanders AR, Sanders SJ, Santangelo SL, Sergeant JA, Schachar R, Schalling M, Schatzberg AF, Scheftner WA, Schellenberg GD, Scherer SW, Schork NJ, Schulze TG, Schumacher J, Schwarz M, Scolnick E, Scott LJ, Shi J, Shilling PD, Shyn SI, Silverman JM, Slager SL, Smalley SL, Smit JH, Smith EN, Sonuga-Barke EJ, St Clair D, State M, Steffens M, Steinhausen HC, Strauss JS, Strohmaier J, Stroup TS, Sutcliffe JS, Szatmari P, Szelinger S, Thirumalai S, Thompson RC, Todorov AA, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Van Os J, Vicente AM, Vieland VJ, Vincent JB, Visscher PM, Walsh CA, Wassink TH, Watson SJ, Weissman MM, Werge T, Wienker TF, Wijsman EM, Willemsen G, Williams N, Willsey AJ, Witt SH, Xu W, Young AH, Yu TW, Zammit S, Zandi PP, Zhang P, Zitman FG, Zöllner S, Devlin B, Kelsoe JR, Sklar P, Daly MJ, O'Donovan MC, Craddock N, Sullivan PF, Smoller JW, Kendler KS, Wray NR, Cardiff University-Medical Research Council (MRC), HudsonAlpha Institute for Biotechnology, The Institute of Psychiatry-King‘s College London, Cornell University-Weill Medical College of Cornell University [New York], Stanford University Medical School, Technische Universität Dresden (TUD)-University Hospital Carl Gustav Carus, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, McGill University-Montreal Children's Hospital, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Stanford University School of Medicine [Stanford], Stanford University [Stanford], Eberhard Karls Universität Tübingen, Friedrich Alexander University [Erlangen-Nürnberg], Università di Bologna [Bologna] (UNIBO), University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Washington University School of Medicine, Ghent University [Belgium] (UGENT), University of Goettingen, CHUM Research Center, Psychiatry and Behavioral Science, Stanford University School of Medicine [CA, USA], Aalborg Psychiatric Hospital, Aarhus University Hospital, Washington University in St Louis, Instituto Nacional de Saude Dr Ricardo Jorge, Oades, Robert D., Guellaen, Georges, Medical Oncology, Epidemiology, Child and Adolescent Psychiatry / Psychology, and Hematology
Subjects: Netherlands Twin Register (NTR), Medizin, Inheritance Patterns, Social Sciences, AUTISM SPECTRUM DISORDERS, nosology, heritability, COMMON SNPS, 0302 clinical medicine, Crohn Disease, SCHIZOPHRENIA, Child, Psychiatric genetics, Genetics & Heredity, MAJOR DEPRESSIVE DISORDER, RISK, 0303 health sciences, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, 120 000 Neuronal Coherence, Mental Disorders, Variants, BIPOLAR DISORDER, ASSOCIATION, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], Psychiatric Disorders, CROHNS-DISEASE, 3. Good health, Schizophrenia, genetic association study, Medical genetics, Major depressive disorder, SNPs, Adult, medicine.medical_specialty, genetic etiology, medical genetics, DEFICIT HYPERACTIVITY DISORDER, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], Heritability, Genetic Heterogeneity, 03 medical and health sciences, Prevalence of mental disorders, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, ddc:61, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, DCN PAC - Perception action and control NCEBP 9 - Mental health, ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Bipolar disorder, Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Genome, Human, Genetic heterogeneity, medicine.disease, schizophrenia, Attention Deficit Disorder with Hyperactivity, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Published: 2013

34. A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans

Author: Palmer, Nicholette D, McDonough, Caitrin W, Hicks, Pamela J, Roh, Bong H, Wing, Maria R, An, S Sandy, Hester, Jessica M, Cooke, Jessica N, Bostrom, Meredith A, Rudock, Megan E, Talbert, Matthew E, Lewis, Joshua P, DIAGRAM Consortium, MAGIC Investigators, Ferrara, Assiamira, Lu, Lingyi, Ziegler, Julie T, Sale, Michele M, Divers, Jasmin, Shriner, Daniel, Adeyemo, Adebowale, Rotimi, Charles N, Ng, Maggie CY, Langefeld, Carl D, Freedman, Barry I, Bowden, Donald W, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, Morris, Andrew P, Dina, Christian, Welch, Ryan P, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S, Thorleifsson, Gudmar, McCulloch, Laura J, Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J, Raychaudhuri, Soumya, McCarroll, Steve A, Langenberg, Claudia, Hofmann, Oliver M, Dupuis, Josée, Qi, Lu, Segrè, Ayellet V, Van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J, Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L, Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P, Charpentier, Guillaume, Chines, Peter S, Cornelis, Marilyn, Couper, David J, Crawford, Gabe, Doney, Alex SF, Elliott, Katherine S, Elliott, Amanda L, Erdos, Michael R, Fox, Caroline S, Franklin, Christopher S, Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J, Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U, Johnson, Paul RV, Jørgensen, Torben, Kao, Wen HL, Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M, Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, Midthjell, Kristian, Morken, Mario A, Narisu, Narisu, Nilsson, Peter, Owen, Katharine R, Payne, Felicity, Perry, John RB, Petersen, Ann-Kristin, Platou, Carl, Proença, Christine, Prokopenko, Inga, Rathmann, Wolfgang, Rayner, N William, Robertson, Neil R, Rocheleau, Ghislain, Roden, Michael, Sampson, Michael J, Saxena, Richa, Shields, Beverley M, Shrader, Peter, Sigurdsson, Gunnar, Sparsø, Thomas, Strassburger, Klaus, Stringham, Heather M, Sun, Qi, Swift, Amy J, Thorand, Barbara, Tichet, Jean, Tuomi, Tiinamaija, Van Dam, Rob M, Van Haeften, Timon W, Van Herpt, Thijs, Van Vliet-Ostaptchouk, Jana V, Walters, G Bragi, Weedon, Michael N, Wijmenga, Cisca, Witteman, Jacqueline, Bergman, Richard N, Cauchi, Stephane, Collins, Francis S, Gloyn, Anna L, Gyllensten, Ulf, Hansen, Torben, Hide, Winston A, Hitman, Graham A, Hofman, Albert, Hunter, David J, Hveem, Kristian, Laakso, Markku, Mohlke, Karen L, Morris, Andrew D, Palmer, Colin NA, Pramstaller, Peter P, Rudan, Igor, Sijbrands, Eric, Stein, Lincoln D, Tuomilehto, Jaakko, Uitterlinden, Andre, Walker, Mark, Wareham, Nicholas J, Watanabe, Richard M, Abecasis, Goncalo R, Boehm, Bernhard O, Campbell, Harry, Daly, Mark J, Hattersley, Andrew T, Hu, Frank B, Meigs, James B, Pankow, James S, Pedersen, Oluf, Wichmann, H-Erich, Barroso, Inês, Florez, Jose C, Frayling, Timothy M, Groop, Leif, Sladek, Rob, Thorsteinsdottir, Unnur, Wilson, James F, Illig, Thomas, Froguel, Philippe, Van Duijn, Cornelia M, Stefansson, Kari, Altshuler, David, Boehnke, Michael, McCarthy, Mark I, Soranzo, Nicole, Wheeler, Eleanor, Glazer, Nicole L, Bouatia-Naji, Nabila, Mägi, Reedik, Randall, Joshua, Johnson, Toby, Elliott, Paul, Rybin, Denis, Henneman, Peter, Dehghan, Abbas, Hottenga, Jouke Jan, Song, Kijoung, Goel, Anuj, Egan, Josephine M, Lajunen, Taina, Doney, Alex, Kanoni, Stavroula, Cavalcanti-Proença, Christine, Kumari, Meena, Timpson, Nicholas J, Zabena, Carina, Ingelsson, Erik, An, Ping, O'Connell, Jeffrey, Luan, Jian'an, Elliott, Amanda, McCarroll, Steven A, Roccasecca, Rosa Maria, Pattou, François, Sethupathy, Praveen, Ariyurek, Yavuz, Barter, Philip, Beilby, John P, Ben-Shlomo, Yoav, Bergmann, Sven, Bochud, Murielle, Bonnefond, Amélie, Borch-Johnsen, Knut, Böttcher, Yvonne, Brunner, Eric, Bumpstead, Suzannah J, Chen, Yii-Der Ida, Chines, Peter, Clarke, Robert, Coin, Lachlan JM, Cooper, Matthew N, Crisponi, Laura, Day, Ian NM, De Geus, Eco JC, Delplanque, Jerome, Fedson, Annette C, Fischer-Rosinsky, Antje, Forouhi, Nita G, Frants, Rune, Franzosi, Maria Grazia, Galan, Pilar, Goodarzi, Mark O, Graessler, Jürgen, Grundy, Scott, Gwilliam, Rhian, Hallmans, Göran, Hammond, Naomi, Han, Xijing, Hartikainen, Anna-Liisa, Hayward, Caroline, Heath, Simon C, Hercberg, Serge, Hicks, Andrew A, Hillman, David R, Hingorani, Aroon D, Hui, Jennie, Hung, Joe, Jula, Antti, Kaakinen, Marika, Kaprio, Jaakko, Kesaniemi, Y Antero, Kivimaki, Mika, Knight, Beatrice, Koskinen, Seppo, Kovacs, Peter, Kyvik, Kirsten Ohm, Lathrop, G Mark, Lawlor, Debbie A, Le Bacquer, Olivier, Lecoeur, Cécile, Li, Yun, Mahley, Robert, Mangino, Massimo, Manning, Alisa K, Martínez-Larrad, María Teresa, McAteer, Jarred B, McPherson, Ruth, Meisinger, Christa, Melzer, David, Meyre, David, Mitchell, Braxton D, Mukherjee, Sutapa, Naitza, Silvia, Neville, Matthew J, Oostra, Ben A, Orrù, Marco, Pakyz, Ruth, Paolisso, Giuseppe, Pattaro, Cristian, Pearson, Daniel, Peden, John F, Pedersen, Nancy L, Perola, Markus, Pfeiffer, Andreas FH, Pichler, Irene, Polasek, Ozren, Posthuma, Danielle, Potter, Simon C, Pouta, Anneli, Province, Michael A, Psaty, Bruce M, Rayner, Nigel W, Rice, Kenneth, Ripatti, Samuli, Rivadeneira, Fernando, Rolandsson, Olov, Sandbaek, Annelli, Sandhu, Manjinder, Sanna, Serena, Sayer, Avan Aihie, Scheet, Paul, Seedorf, Udo, Sharp, Stephen J, Shields, Beverley, Sijbrands, Eric JG, Silveira, Angela, Simpson, Laila, Singleton, Andrew, Smith, Nicholas L, Sovio, Ulla, Swift, Amy, Syddall, Holly, Syvänen, Ann-Christine, Tanaka, Toshiko, Tönjes, Anke, Uitterlinden, André G, Van Dijk, Ko Willems, Varma, Dhiraj, Visvikis-Siest, Sophie, Vitart, Veronique, Vogelzangs, Nicole, Waeber, Gérard, Wagner, Peter J, Walley, Andrew, Ward, Kim L, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Witteman, Jaqueline CM, Yarnell, John WG, Zelenika, Diana, Zethelius, Björn, Zhai, Guangju, Zhao, Jing Hua, Zillikens, M Carola, Borecki, Ingrid B, Loos, Ruth JF, Meneton, Pierre, Magnusson, Patrik KE, Nathan, David M, Williams, Gordon H, Silander, Kaisa, Salomaa, Veikko, Smith, George Davey, Bornstein, Stefan R, Schwarz, Peter, Spranger, Joachim, Karpe, Fredrik, Shuldiner, Alan R, Cooper, Cyrus, Dedoussis, George V, Serrano-Ríos, Manuel, Lind, Lars, Palmer, Lyle J, Franks, Paul W, Ebrahim, Shah, Marmot, Michael, Kao, WH Linda, Pramstaller, Peter Paul, Wright, Alan F, Stumvoll, Michael, Hamsten, Anders, Buchanan, Thomas A, Valle, Timo T, Rotter, Jerome I, Siscovick, David S, Penninx, Brenda WJH, Boomsma, Dorret I, Deloukas, Panos, Spector, Timothy D, Ferrucci, Luigi, Cao, Antonio, Scuteri, Angelo, Schlessinger, David, Uda, Manuela, Ruokonen, Aimo, Jarvelin, Marjo-Riitta, Waterworth, Dawn M, Vollenweider, Peter, Peltonen, Leena, Mooser, Vincent, Sladek, Robert, Center for Liver, Digestive and Metabolic Diseases (CLDM), Palmer, Nd, Mcdonough, Cw, Hicks, Pj, Roh, Bh, Wing, Mr, An, S, Hester, Jm, Cooke, Jn, Bostrom, Ma, Rudock, Me, Talbert, Me, Lewis, Jp, Diagram, Consortium, Magic, Investigator, Ferrara, A, Lu, L, Ziegler, Jt, Sale, Mm, Divers, J, Shriner, D, Adeyemo, A, Rotimi, Cn, Ng, Mc, Langefeld, Cd, Freedman, Bi, Bowden, Dw, Voight, Bf, Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, Sladek, R., Medical Research Council (MRC), Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Langenberg, Claudia [0000-0002-5017-7344], Griffin, Simon [0000-0002-2157-4797], Wareham, Nicholas [0000-0003-1422-2993], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Apollo - University of Cambridge Repository, DIAGRAM Consortium, MAGIC Investigators, Johnson, T., Bergman, S., Bochud, M., Waeber, G., and Vollenweider, P.
Subjects: Netherlands Twin Register (NTR), Male, Adult, African Americans/genetics, Aged, Case-Control Studies, Cohort Studies, Diabetes Mellitus, Type 2/ethnology, Diabetes Mellitus, Type 2/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Validation Studies as Topic, Medicin och hälsovetenskap, Linkage disequilibrium, Genetic Screens, endocrine system diseases, lcsh:Medicine, Genome-wide association study, Medical and Health Sciences, 0302 clinical medicine, Endocrinology, Genome Sequencing, lcsh:Science, Medicine(all), Genetics, African Americans, 0303 health sciences, education.field_of_study, INSULIN-RESISTANCE, Multidisciplinary, Agricultural and Biological Sciences(all), LARGE-SCALE ASSOCIATION, STAGE RENAL-DISEASE, COMMON VARIANTS, Genomics, Medicine, Research Article, SUSCEPTIBILITY LOCI, General Science & Technology, Population, Single-nucleotide polymorphism, Biology, DIAGRAM Consortium, 03 medical and health sciences, MAGIC Investigators, SDG 3 - Good Health and Well-being, Genetic linkage, MD Multidisciplinary, Genome-Wide Association Studies, SNP, ddc:610, education, Genotyping, 030304 developmental biology, Diabetic Endocrinology, LINKAGE ANALYSIS, Biochemistry, Genetics and Molecular Biology(all), lcsh:R, TCF7L2 GENE, Case-control study, Computational Biology, nutritional and metabolic diseases, Human Genetics, Diabetes Mellitus Type 2, Stage renal-disease, large-scale association, Susceptibility loci, Insulin-resistance, Fasting glucose, Tissue factor, Homeodomain protein, Linkage analysis, Common variants, TCF7L2 gene, Black or African American, Diabetes Mellitus, Type 2, TISSUE FACTOR, Genetics of Disease, HOMEODOMAIN PROTEIN, Genetic Polymorphism, lcsh:Q, Genome Expression Analysis, 030217 neurology & neurosurgery, Population Genetics, FASTING GLUCOSE
Abstract: African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P
Published: 2012

35. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women

Author: Amelie Bonnefond, Nancy Heard-Costa, Eleftheria Zeggini, Anna Gloyn, LAURA CRISPONI, Eco De Geus, Michael Weedon, Torben Jørgensen, Jaakko Kaprio, Iva Miljkovic, Amanda Bennett, Yurii Aulchenko, Michael Stumvoll, Andrew Hattersley, Christian Dina, Sophie Visvikis-Siest, Udo Seedorf, Vilmundur Gudnason, Michael Marmot, Mika Kivimaki, Mary Feitosa, Danielle Posthuma, Claudia Langenberg, Stavroula Kanoni, Cyrus Cooper, Meena Kumari, Peter Kovacs, Debbie A Lawlor, Inga Prokopenko, Rafn Benediktsson, Stephen Kritchevsky, Philippe Froguel, Cornelia Van Duijn, Nita Forouhi, Anne B. Newman, Ko Willems van Dijk, John Carr, Reedik Mägi, Sutapa Mukherjee, Lyle John Palmer, Francois Pattou, L. Adrienne Cupples, Paul Franks, Paul Elliott, Albert Vernon Smith, MANUELA UDA, Kirsten Ohm Kyvik, Manuel Serrano Ríos, Richard Bergman, Gonneke Willemsen, Cecilia Lindgren, Igor Rudan, Human genetics, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Institute for Molecular Medicine Finland, Research Group Ripatti Samuli, Hjelt Institute (-2014), Department of Public Health, Biostatistics Helsinki, Complex Disease Genetics, Genetic Epidemiology, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, GIANT Consortium, MAGIC Consortium, GLGC Consortium, Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, AU., Wheeler, E., Glazer, NL., Bouatia-Naji, N., Gloyn, AL., Lindgren, CM., Mägi, R., Morris, AP., Randall, J., Johnson, T., Elliott, P., Rybin, D., Thorleifsson, G., Steinthorsdottir, V., Henneman, P., Grallert, H., Dehghan, A., Hottenga, JJ., Franklin, CS., Navarro, P., Song, K., Goel, A., Perry, JR., Egan, JM., Lajunen, T., Grarup, N., Sparsø, T., Doney, A., Voight, BF., Stringham, HM., Li, M., Kanoni, S., Shrader, P., Cavalcanti-Proença, C., Kumari, M., Qi, L., Timpson, NJ., Gieger, C., Zabena, C., Rocheleau, G., Ingelsson, E., An, P., O'Connell, J., Luan£££Jian'an£££ J., Elliott, A., McCarroll, SA., Payne, F., Roccasecca, RM., Pattou, F., Sethupathy, P., Ardlie, K., Ariyurek, Y., Balkau, B., Barter, P., Beilby, JP., Ben-Shlomo, Y., Benediktsson, R., Bennett, AJ., Bergmann, S., Bochud, M., Boerwinkle, E., Bonnefond, A., Bonnycastle, LL., Borch-Johnsen, K., Böttcher, Y., Brunner, E., Bumpstead, SJ., Charpentier, G., Chen, YD., Chines, P., Clarke, R., Coin, LJ., Cooper, MN., Cornelis, M., Crawford, G., Crisponi, L., Day, IN., de Geus EJ., Delplanque, J., Dina, C., Erdos, MR., Fedson, AC., Fischer-Rosinsky, A., Forouhi, NG., Fox, CS., Frants, R., Franzosi, MG., Galan, P., Goodarzi, MO., Graessler, J., Groves, CJ., Grundy, S., Gwilliam, R., Gyllensten, U., Hadjadj, S., Hallmans, G., Hammond, N., Han, X., Hartikainen, AL., Hassanali, N., Hayward, C., Heath, SC., Hercberg, S., Herder, C., Hicks, AA., Hillman, DR., Hingorani, AD., Hofman, A., Hui, J., Hung, J., Isomaa, B., Johnson, PR., Jørgensen, T., Jula, A., Kaakinen, M., Kaprio, J., Kesaniemi, YA., Kivimaki, M., Knight, B., Koskinen, S., Kovacs, P., Kyvik, KO., Lathrop, GM., Lawlor, DA., Le Bacquer, O., Lecoeur, C., Li, Y., Lyssenko, V., Mahley, R., Mangino, M., Manning, AK., Martínez-Larrad£££María Teresa£££ MT., McAteer, JB., McCulloch, LJ., McPherson, R., Meisinger, C., Melzer, D., Meyre, D., Mitchell, BD., Morken, MA., Mukherjee, S., Naitza, S., Narisu, N., Neville, MJ., Oostra, BA., Orrù, M., Pakyz, R., Palmer, CN., Paolisso, G., Pattaro, C., Pearson, D., Peden, JF., Pedersen, NL., Perola, M., Pfeiffer, AF., Pichler, I., Polasek, O., Posthuma, D., Potter, SC., Pouta, A., Province, MA., Psaty, BM., Rathmann, W., Rayner, NW., Rice, K., Ripatti, S., Rivadeneira, F., Roden, M., Rolandsson, O., Sandbaek, A., Sandhu, M., Sanna, S., Sayer, AA., Scheet, P., Scott, LJ., Seedorf, U., Sharp, SJ., Shields, B., Sigurðsson, G., Sijbrands, EJ., Silveira, A., Simpson, L., Singleton, A., Smith, NL., Sovio, U., Swift, A., Syddall, H., Syvänen, AC., Tanaka, T., Thorand, B., Tichet, J., Tönjes, A., Tuomi, T., Uitterlinden, AG., van Dijk KW., van Hoek, M., Varma, D., Visvikis-Siest, S., Vitart, V., Vogelzangs, N., Waeber, G., Wagner, PJ., Walley, A., Walters, GB., Ward, KL., Watkins, H., Weedon, MN., Wild, SH., Willemsen, G., Witteman, JC., Yarnell, JW., Zeggini, E., Zelenika, D., Zethelius, B., Zhai, G., Zhao, JH., Zillikens, MC., Borecki, IB., Loos, RJ., Meneton, P., Magnusson, PK., Nathan, DM., Williams, GH., Hattersley, AT., Silander, K., Salomaa, V., Smith, GD., Bornstein, SR., Schwarz, P., Spranger, J., Karpe, F., Shuldiner, AR., Cooper, C., Dedoussis, GV., Serrano-Ríos, M., Morris, AD., Lind, L., Palmer, LJ., Hu, FB., Franks, PW., Ebrahim, S., Marmot, M., Kao, WH., Pankow, JS., Sampson, MJ., Kuusisto, J., Laakso, M., Hansen, T., Pedersen, O., Pramstaller, PP., Wichmann, HE., Illig, T., Rudan, I., Wright, AF., Stumvoll, M., Campbell, H., Wilson, JF., Hamsten, A., Bergman, RN., Buchanan, TA., Collins, FS., Mohlke, KL., Tuomilehto, J., Valle, TT., Altshuler, D., Rotter, JI., Siscovick, DS., Penninx, BW., Boomsma, ID., Deloukas, P., Spector, TD., Frayling, TM., Ferrucci, L., Kong, A., Thorsteinsdottir, U., Stefansson, K., van Duijn CM., Aulchenko, YS., Cao, A., Scuteri, A., Schlessinger, D., Uda, M., Ruokonen, A., Jarvelin, MR., Waterworth, DM., Vollenweider, P., Peltonen, L., Mooser, V., Abecasis, RG., Wareham, NJ., Sladek, R., Froguel, P., Watanabe, RM., Meigs, JB., Groop, L., Boehnke, M., McCarthy, MI., Florez, JC., Barroso£££Inês£££ I., Feitosa, Mary [0000-0002-0933-2410], Heard-Costa, Nancy [0000-0001-9730-0306], Newman, Anne B [0000-0002-0106-1150], Miljkovic, Iva [0000-0002-3155-9777], Kritchevsky, Stephen B [0000-0003-3336-6781], Carr, J Jeffrey [0000-0002-4398-8237], Gudnason, Vilmunder [0000-0001-5696-0084], Cupples, L Adrienne [0000-0003-0273-7965], Apollo - University of Cambridge Repository, and Medical Research Council (MRC)
Subjects: Male, Netherlands Twin Register (NTR), Cancer Research, Adipose tissue, Genome-wide association study, QH426-470, FTO gene, Body Mass Index, 0302 clinical medicine, Genetics (clinical), TISSUE DISTRIBUTION, GENE-EXPRESSION, 2. Zero hunger, ATHEROSCLEROSIS MESA, 0303 health sciences, INSULIN-RESISTANCE, Sex Characteristics, MAGIC Consortium, Adult, Aged, Cytokines/genetics, European Continental Ancestry Group, Female, Genome-Wide Association Study, HapMap Project, Humans, Intra-Abdominal Fat, Lysophospholipase/genetics, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proteins/genetics, Subcutaneous Fat, Abdominal, 3142 Public health care science, environmental and occupational health, CARDIOVASCULAR-DISEASE, OBESITY, Cytokines, Medicine, Lysophospholipase, Research Article, medicine.medical_specialty, Waist, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, 030209 endocrinology & metabolism, HIP RATIO, Biology, White People, GLGC Consortium, 03 medical and health sciences, Insulin resistance, Internal medicine, GIANT Consortium, medicine, Genetics, CORONARY-HEART-DISEASE, ddc:610, Molecular Biology, PERICARDIAL FAT, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0604 Genetics, Proteins, nutritional and metabolic diseases, medicine.disease, Obesity, Endocrinology, RISK-FACTORS, Body mass index, Developmental Biology
Abstract: Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ∼2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1×10E-09), previously identified in association with waist–hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9×10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6×10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist–hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits., Author Summary Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. We quantified subcutaneous and visceral fat in more than 10,000 women and men who also had genome-wide association data available. Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, near the THNSL2 gene. These findings were not observed in men. We also interrogated our data for the 14 recently published loci for body fat distribution (measured by waist–hip ratio adjusted for BMI); associations were observed for 7 of these loci, most notably for VAT/SAT ratio. We conclude that genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not uncovered in large-scale GWAS of anthropometric traits.
Published: 2012

36. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author: Fredrik Karpe, Ivonne Jarick, Julius S. Ngwa, Alan F. Wright, Robert Luben, Aaron R. Folsom, Sailaja Vedantam, Veikko Salomaa, Markku J. Savolainen, Robert Clarke, Shah Ebrahim, Thomas A. Buchanan, Mao Fu, Albert Hofman, Philippe Goyette, Camilla H. Sandholt, Fabio Macciardi, Elizabeth K. Speliotes, Barbara McKnight, Anne McCarthy, Mika Kaehoenen, Christian Gieger, Jorma S. A. Viikari, Nicholas J. Timpson, Kirsti Kvaløy, Douglas F. Levinson, Toby Johnson, Cornelia M. van Duijn, Samuli Ripatti, Andrew A. Hicks, Niina Pellikka, Charles C. White, Leena Peltonen, Reedik Maegi, John-Olov Jansson, Qunyuan Zhang, Claudia Lamina, Robert C. Kaplan, Peter M. Visscher, Laura J. Scott, Claes Ohlsson, Brian Thomson, Jubao Duan, Heikki V. Huikuri, Stephen O'Rahilly, Anette P. Gjesing, David P. Strachan, Caroline S. Fox, Sekar Kathiresan, Anna-Liisa Hartikainen, Johannes Kettunen, Maris Teder-Laving, Erik Ingelsson, Mario A. Morken, Peter Kovacs, Elisabeth Widen, Caroline Hayward, Eleanor Wheeler, Jing Hua Zhao, Vilmundur Gudnason, Panos Deloukas, Jacqueline C. M. Witteman, Gert-Jan B. van Ommen, Eric Boerwinkle, Martin Wabitsch, Christian Hengstenberg, Beverley Balkau, Thor Aspelund, Neelam Hassanali, Paul M. Ridker, Nicole L. Glazer, Joyce B. J. van Meurs, Michel Marre, Alan James, Ben A. Oostra, David Meyre, Ida Surakka, Stefan Schreiber, Nigel W. Rayner, Heribert Schunkert, Thomas Quertermous, Stefan Gustafsson, Peter Kraft, Benjamin F. Voight, Irene Pichler, Olle Melander, Ozren Polasek, Antti Jula, Alan R. Sanders, Andrew R. Wood, Yoav Ben-Shlomo, Thomas Illig, Jianjun Liu, Gerard Waeber, André G. Uitterlinden, Torben Hansen, Helene Alavere, André Scherag, Paolo Manunta, Johannes Hebebrand, Themistocles L. Assimes, Stefan R. Bornstein, Jaakko Tuomilehto, Morris Brown, Jianfeng Xu, Yii-Der Ida Chen, Nancy L. Heard-Costa, Cristen J. Willer, Henrik Greonberg, Guillaume Lettre, John R. Thompson, Inês Barroso, John R. B. Perry, Andreas Ziegler, James F. Wilson, Christopher J. O'Donnell, Maurizio F. Facheris, Robert Lawrence, Jan Smit, Lyle J. Palmer, Ulf Gyllensten, Richard B. Hayes, Shengxu Li, Barbara Ludwig, Larry D. Atwood, Valgerdur Steinthorsdottir, Sabine Schipf, Jouko Saramies, Tanja Boes, Martin Ridderstråle, Jennie Hui, Lina Zgaga, Susann Scherag, Alexandra I. F. Blakemore, Marjolein Peters, Timo T. Valle, Nelson B. Freimer, Kay-Tee Khaw, Amy J. Swift, Michael Stumvoll, Miriam F. Moffatt, Cecilia M. Lindgren, Ayellet V. Segrè, Neil Robertson, Richard N. Bergman, Francis S. Collins, Ryan P. Welch, Mari-Liis Tammesoo, Devin Absher, Tamara B. Harris, Kari E. North, Manuela Uda, Karen L. Mohlke, Inga Prokopenko, Per Hall, Gudmar Thorleifsson, Marjo-Riitta Järvelin, Guillaume Paré, Stefan Gaget, G. Bragi Walters, Michael N. Weedon, Jean-Claude Tardif, Mary F. Feitosa, Anke Toenjes, Ken K. Ong, Cécile Lecoeur, Paavo Zitting, David S. Siscovick, Chih-Mei Chen, Peter Almgren, Anneli Pouta, Philippe Froguel, Pekka Jousilahti, Jaakko Kaprio, Maria Teresa Sciarrone Alibrandi, Sophie van Wingerden, Steven A. McCarroll, Oluf Pedersen, Shaun Purcell, Veronique Vitart, Leena Kinnunen, Markus Perola, Jacques S. Beckmann, Vincent Vatin, Christopher J. Groves, Zoltán Kutalik, Lu Qi, Volker Hoesel, Seppo Koskinen, Suzanne Rafelt, Anke Hinney, Annette Peters, David Schlessinger, Eero Kajantie, Jian Yang, Nicholas G. Martin, Joshua W. Knowles, Kristian Midthjell, Olivier Lantieri, Dorret I. Boomsma, Harry Campbell, Ulrich John, Kirsi H. Pietilaeinen, George Davey Smith, Carl G. P. Platou, Sarah H. Wild, Patricia B. Munroe, Iris M. Heid, Diana Marek, Michael Boehnke, Andres Metspalu, Hana Lango Allen, Peter Rzehak, Christine Cavalcanti-Proença, M. Carola Zillikens, Åsa Johansson, Anuj Goel, Andrew T. Hattersley, Massimo Mangino, Michael E. Goddard, Tim D. Spector, Winfried Rief, Jonathan Tyrer, Lachlan J. M. Coin, Peter P. Pramstaller, Narisu Narisu, John Beilby, Jonathan Stephens, Christina Barlassina, Pamela Fischer-Posovszky, Brenda W.J.H. Penninx, Kaisa Silander, Richard H. Myers, Jouke-Jan Hottenga, Eric E. Schadt, Francesco P. Cappuccio, Martin den Heijer, Fernando Rivadeneira, Lindsay L. Waite, Wilmar Igl, Igor Rudan, Manjinder S. Sandhu, Debbie A Lawlor, Kristian Hveem, Susanna Wiegand, Mari Nelis, Thomas Reinehr, Elisabeth Thiering, Inke R. Koenig, Stephan B. Felix, Fredrik Wiklund, Ian N. M. Day, Willem H. Ouwehand, Peter Schwarz, Richard M. Watanabe, Keri L. Monda, Kari Stefansson, Gudny Eiriksdottir, H-Erich Wichmann, Jianxin Shi, Najaf Amin, Carlos Iribarren, Heiko Krude, Dale R. Nyholt, Lenore J. Launer, Stephen J. Chanock, Harald Grallert, Hugh Watkins, Juergen Graessler, Tsegaselassie Workalemahu, Jeanette Erdmann, Mattias Lorentzon, Leif Groop, Teresa Ferreira, Chiara Lanzani, Johanna Kuusisto, Johan G. Eriksson, Tõnu Esko, Torben Jørgensen, Robert J. Weyant, Michael Preuss, Lambertus A. Kiemeney, Daniel I. Chasman, Daniel R. Witte, Kevin B. Jacobs, Nicole Soranzo, John M. C. Connell, Soumya Raychaudhuri, Jian'an Luan, Joshua C. Randall, Joachim Heinrich, Anthony J. Balmforth, Eva Fisher, Elizabeth S. Jewell, Alice M. Arnold, Nele Friedrich, Olli T. Raitakari, Henri Wallaschofski, Jeffrey R. O'Connell, Terho Lehtimaeki, Marika Kaakinen, Heather M. Stringham, Bo Isomaa, I. Sadaf Farooqi, Anna L. Dixon, Anne U. Jackson, Mark I. McCarthy, Lori L. Bonnycastle, Aila Rissanen, Joel N. Hirschhorn, Nilesh J. Samani, Aimo Ruokonen, Frank B. Hu, L. Adrienne Cupples, Amanda J. Bennett, Shamika Ketkar, Ruth J. F. Loos, Nicholas J. Wareham, Tiinamaija Tuomi, Timothy M. Frayling, Ulla Sovio, Georg Homuth, Liming Liang, Heiner Boeing, Unnur Thorsteinsdottir, Ingrid B. Borecki, Danielle M. Greenawalt, Rosanda Mulić, Ivana Kolcic, Talin Haritunians, Mark J. Caulfield, Marja-Liisa Lokki, Tanya M. Teslovich, Paul Elliott, Matt Neville, Nilanjan Chatterjee, Albert V. Smith, Andrew P. Morris, Fabio Busonero, Gonçalo R. Abecasis, Jaana Laitinen, Michael R. Erdos, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Pablo V. Gejman, Alan R. Shuldiner, Serena Sanna, David J. Hunter, Sonja I. Berndt, Carla I. G. Vogel, Alistair S. Hall, Karol Estrada, Sven Bergmann, Thomas Meitinger, Gonneke Willemsen, Andrew C. Heath, Katja K.H. Aben, Markku Laakso, Juha Sinisalo, Tuomas O. Kilpelaenen, Mark E. Cooper, Heike Biebermann, Eco J. C. de Geus, Grant W. Montgomery, Sophie Visvikis-Siest, Thomas W. Winkler, Ju-Hyun Park, Alex N. Parker, Peter S. Chines, James Nemesh, Nabila Bouatia-Naji, Wendy L. McArdle, Roberto Elosua, Markku S. Nieminen, Psychiatry, NCA - Anxiety & Depression, EMGO - Mental health, Epidemiology, Internal Medicine, Clinical Genetics, Radiology & Nuclear Medicine, Erasmus MC other, Public Health, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, MAGIC, Procardis Consortium, Medical Research Council (MRC), Speliotes, Ek, Willer, Cj, Berndt, Si, Monda, Kl, Thorleifsson, G, Jackson, Au, Allen, Hl, Lindgren, Cm, Luan, J, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Qi, L, Workalemahu, T, Heid, Im, Steinthorsdottir, V, Stringham, Hm, Weedon, Mn, Wheeler, E, Wood, Ar, Ferreira, T, Weyant, Rj, Segrè, Av, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Gustafsson, S, Kilpeläinen, To, Yang, J, BOUATIA NAJI, N, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Amin, N, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, HEARD COSTA, Nl, Hoesel, V, Hottenga, Jj, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Narisu, N, Perry, Jr, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, Lj, Timpson, Nj, Tyrer, Jp, VAN WINGERDEN, S, Watanabe, Rm, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Almgren, P, Arnold, Am, Aspelund, T, Atwood, Ld, Balkau, B, Balmforth, Aj, Bennett, Aj, BEN SHLOMO, Y, Bergman, Rn, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bonnycastle, Ll, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Campbell, H, Cappuccio, Fp, CAVALCANTI PROENÇA, C, Chen, Yd, Chen, Cm, Chines, P, Clarke, R, Coin, L, Connell, J, Day, In, DEN HEIJER, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, Mr, Eriksson, Jg, Facheris, Mf, Felix, Sb, FISCHER POSOVSZKY, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gieger, C, Gjesing, Ap, Goel, A, Goyette, P, Grallert, H, Grässler, J, Greenawalt, Dm, Groves, Cj, Gudnason, V, Guiducci, C, Hartikainen, Al, Hassanali, N, Hall, A, Havulinna, A, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jørgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Lehtimäki, T, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, Paolo, Marek, D, Marre, M, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, Gw, Morken, Ma, Morris, Ap, Mulic, R, Ngwa, J, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Robertson, Nr, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, M, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, D, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, Aj, Tammesoo, Ml, Tardif, Jc, TEDER LAVING, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, Tuomi, T, VAN MEURS, Jb, VAN OMMEN, Gj, Vatin, V, Viikari, J, VISVIKIS SIEST, S, Vitart, V, Vogel, Ci, Voight, Bf, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, I, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, M, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, J, Boeing, H, Boerwinkle, E, Boomsma, Di, Caulfield, Mj, Chanock, Sj, Collins, F, Cupples, La, Smith, Gd, Erdmann, J, Froguel, P, Grönberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, Tb, Hattersley, At, Hayes, Rb, Heinrich, J, Hu, Fb, Hveem, K, Illig, T, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Laakso, M, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Pedersen, O, Penninx, Bw, Peters, A, Pramstaller, Pp, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, Tt, Wabitsch, M, Waeber, G, Wareham, Nj, Watkins, H, Procardis, Consortium, Wilson, Jf, Wright, Af, Zillikens, Mc, Chatterjee, N, Mccarroll, Sa, Purcell, S, Schadt, Ee, Visscher, Pm, Assimes, Tl, Borecki, Ib, Deloukas, P, Fox, C, Groop, Lc, Haritunians, T, Hunter, Dj, Kaplan, Rc, Mohlke, Kl, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, VAN DUIJN, Cm, Wichmann, He, Frayling, Tm, Thorsteinsdottir, U, Abecasis, Gr, Barroso, I, Boehnke, M, Stefansson, K, North, Ke, Mccarthy, Mi, Hirschhorn, Jn, Ingelsson, E, and Loos, Rj
Subjects: Netherlands Twin Register (NTR), Medizin, Genome-wide association study, Aetiology, screening and detection [ONCOL 5], FTO gene, Body Mass Index, 0302 clinical medicine, SH2B1, GASTRIC-INHIBITORY POLYPEPTIDE, ADULT OBESITY, Glucose homeostasis, Body Size, GENETICS & HEREDITY, 2. Zero hunger, Genetics, Genetics & Heredity, RISK, 0303 health sciences, Neuronal growth regulator 1, Genetics of obesity, COMMON VARIANTS, Chromosome Mapping, 11 Medical And Health Sciences, Body Height/genetics, Body Size/genetics, Body Weight/genetics, European Continental Ancestry Group/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Humans, Obesity/genetics, Polymorphism, Single Nucleotide, FAT MASS, Body Height/*genetics *Body Mass Index Body Size/genetics Body Weight/*genetics *Chromosome Mapping European Continental Ancestry Group/genetics Genetic Predisposition to Disease/genetics Genome-Wide Association Study Humans Obesity/genetics Polymorphism, Single Nucleotide, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, MELANOCORTIN-4 RECEPTOR GENE, Life Sciences & Biomedicine, European Continental Ancestry Group, EARLY-ONSET, 030209 endocrinology & metabolism, Locus (genetics), Biology, Article, White People, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, SDG 3 - Good Health and Well-being, body mass index, genome-wide association, meta-analysis, Genetic Predisposition to Disease, Obesity, GENOME-WIDE ASSOCIATION, FTO GENE, 030304 developmental biology, Science & Technology, genome-wide association gastric-inhibitory polypeptide melanocortin-4 receptor gene glucose-homeostasis common variants adult obesity early-onset fat mass risk metaanalysis, Body Weight, 06 Biological Sciences, MAGIC, Body Height, GLUCOSE-HOMEOSTASIS, Procardis Consortium, Body mass index, Developmental Biology
Abstract: Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS index (P < 5-10-8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly aSociated loci may provide new insights into human body weight regulation. © 2010 Nature America, Inc. All rights reserved.
Published: 2010

37. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

Author: Myocardial Infarction Genetics, The complete list, Sekar, Kathiresan, Voight, Benjamin F., Shaun, Purcell, Kiran, Musunuru, Diego, Ardissino, Mannucci, Pier M., Sonia, Anand, Engert, James C., Samani, Nilesh J., Heribert, Schunkert, Jeanette, Erdmann, Reilly, Muredach P., Rader, Daniel J., Thomas, Morgan, Spertus, John A., Monika, Stoll, Girelli, Domenico, Mckeown, Pascal P., Patterson, Chris C., Siscovick, David S., O'Donnell, Christopher J., Roberto, Elosua, Leena, Peltonen, Veikko, Salomaa, Schwartz, Stephen M., Olle, Melander, David, Altshuler, Thrombosis Italian Atherosclerosis, Vascular Biology Study, Pier Angelica Merlini, Carlo, Berzuini, Luisa, Bernardinelli, Flora, Peyvandi, Marco, Tubaro, Patrizia, Celli, Maurizio, Ferrario, Raffaela, Fetiveau, Nicola, Marziliano, Giorgio, Casari, Michele, Galli, Ribichini, Flavio Luciano, Marco, Rossi, Francesco, Bernardi, Pietro, Zonzin, Alberto, Piazza, Heart Attack Risk, Jean, Yee, Yechiel, Friedlander, Registre Gironi del, Jaume, Marrugat, Gavin, Lucas, Isaac, Subirana, Joan, Sala, Rafael, Ramos, Massachusetts General Hospital, Meigs, James B., Gordon, Williams, Nathan, David M., Macrae, Calum A., F. I. N., Havulinna, Aki S., Malmo, Diet, Cancer, Study, Goran, Berglund, Stage, 1 data, Hirschhorn, Joel N., Rosanna, Asselta, Stefano, Duga, Marta, Spreafico, Daly, Mark J., Copy number variant, James, Nemesh, Korn, Joshua M., Mccarroll, Steven A., Stage, 1 phenotype, Stage, 1 genome wide, Aarti, Surti, Candace, Guiducci, Lauren, Gianniny, Daniel, Mirel, Melissa, Parkin, Noel, Burtt, Gabriel, Stacey B., Replication, Studies, Thompson, John R., Braund, Peter S., Wright, Benjamin J., Balmforth, Anthony J., Ball, Stephen G., Hall, Alistair S., Wellcome Trust Case, German MI Family, Patrick Linsel Nitschke, Wolfgang, Lieb, Andreas, Ziegler, König, Inke R., Christian, Hengstenberg, Marcus, Fischer, Klaus, Stark, Anika, Grosshennig, Michael, Preuss, Erich Wichmann, H., Stefan, Schreiber, Cardiogenics, Willem, Ouwehand, Panos, Deloukas, Michael, Scholz, Francois, Cambien, C. a. r. d. i. o. g. e. n. i. c. s., P. e. n. n. C. A. T., Mingyao, Li, Zhen, Chen, Robert, Wilensky, William, Matthai, Atif, Qasim, Hakonarson, Hakon H., Joe, Devaney, Mary Susan Burnett, Pichard, Augusto D., Kent, Kenneth M., Lowell, Satler, Lindsay, Joseph M., Ron, Waksman, Epstein, Stephen E., Acute Myocardial Infarction, Thomas, Scheffold, Klaus, Berger, Andreas, Huge, Verona Heart Study, Domenico, Girelli, Martinelli, Nicola, Olivieri, Oliviero, Corrocher, Roberto, Mid America Heart Institute, Irish Family Study, d. e. C. O. D., Hilma, Hólm, Gudmar, Thorleifsson, Unnur, Thorsteinsdottir, Kari, Stefansson, I. N. T., Ron, Do, Changchun, Xie, Gen, M. I., David, Siscovick, Kathiresan, S, Altschuler, D, Anand, S, Ardissino, D, Asselta, R, Ball, Sg, Balmforth, Aj, Berger, K, Berglund, G, Bernardi, F, Bernardinelli, L, Berzuini, C, Braund, P, Burnett, M, Burtt, N, Cambien, F, Casari, GIORGIO NEVIO, Celli, P, Chen, Z, Corrocher, R, Daly, Mj, Deloukas, P, Devaney, J, Do, R, Duga, S, Elosua, R, Engert, Jc, Epstein, Se, Erdmann, J, Ferrario, M, Fetiveau, R, Fischer, M, Friedlander, Y, Gabriel, Sb, Galli, M, Gianniny, L, Girelli, D, Grosshennig, A, Guiducci, C, Hakonarson, Hh, Hall, A, Havulinna, A, Hengstenberg, C, Hirschhorn, Jn, Holm, H, Huge, A, Kent, Km, Konig, Ir, Korn, Jm, Li, M, Lieb, W, Lindsay, Jm, Linsel Nitschke, P, Lucas, G, Macrae, Ca, Mannucci, Pm, Marrugat, J, Martinelli, N, Marziliano, N, Matthai, W, Mccarroll, Sa, Mckeown, Pp, Meigs, Jb, Melander, O, Merlini, Pa, Mirel, D, Morgan, T, Musunuru, K, Nathan, Dm, Nemesh, J, O'Donnell, Cj, Olivieri, O, Ouwehand, W, Parkin, M, Patterson, Cc, Peltonen, L, Peyvandi, F, Piazza, A, Pichard, Ad, Preuss, M, Purcell, S, Qasim, A, Rader, Dj, Ramos, R, Reilly, Mp, Ribichini, F, Rossi, M, Sala, J, Salomaa, V, Samani, Nj, Satler, L, Scheffold, T, Scholz, M, Schreiber, S, Schunkert, H, Schwartz, Sm, Siscovick, D, Spertus, Ja, Spreafico, M, Stark, K, Stefansson, K, Stoll, M, Subirana, I, Surti, A, Thompson, Jr, Thorleifsson, G, Thorsteinsdottir, U, Tubaro, M, Voight, Bf, Waksman, R, Wichmann, He, Wilensky, R, Williams, G, Wright, Bj, Xie, C, Yee, J, Ziegler, A, and Zonzin, P.
Subjects: Adult, Male, copy number variants (CNVs), Gene Dosage, Myocardial Infarction, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, 030204 cardiovascular system & hematology, Biology, Bioinformatics, association study, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, myocardial infarction with single, Gene Frequency, Risk Factors, Genetics cardiovascular diseases, genome-wide association, single nucleotide polymorphisms (SNPs), association with early-onset myocardial infarction, Genetics, Humans, Genetic Predisposition to Disease, Copy-number variation, Age of Onset, Gene, Allele frequency, 030304 developmental biology, 0303 health sciences, myocardial infarction, SNPs, Genome-wide association, nucleotide polymorphisms, Middle Aged, Genetic epidemiology, Case-Control Studies, Mutation, Female, Age of onset, Algorithms, Genome-Wide Association Study
Abstract: We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1, 2, 3, 4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.
Published: 2009

38. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

Author: Seppo Koskinen, Christian Herder, Daniel I. Chasman, Andrew R. Wood, Jonna L. Grimsby, J.F. Wilson, Day Inm., Massimo Mangino, Gonneke Willemsen, Robert W. Mahley, Cristian Pattaro, Nicole L. Glazer, T.B. Harris, Irene Pichler, M S Sandhu, D. van Heemst, Christine Proença, Martha Ganser, Robert A. Hegele, Richa Saxena, Eleftheria Zeggini, Markku Laakso, Peter Kraft, Judith B. Borja, Karen L. Mohlke, J B Richards, de Geus Ejc., Robert Sladek, Cristen J. Willer, Samy Hadjadj, S.M. Boekholdt, Gina M. Peloso, Kijoung Song, Sutapa Mukherjee, Gudmar Thorleifsson, Winston Hide, Mark I. McCarthy, Ruth E. Pakyz, Marian Beekman, Ayellet V. Segrè, Inga Prokopenko, Ping An, George Dedoussis, Danielle Posthuma, Jeanette Erdmann, Simon J. Griffin, Nilesh J. Samani, Inke R. König, Frank B. Hu, Lokki M-L., David M. Evans, Xiaohui Li, Valgerdur Steinthorsdottir, Aimo Ruokonen, A Pouta, Kerrin S. Small, Cecilia M. Lindgren, O Le Bacquer, Xijing Han, Florian Kronenberg, E Katsareli, Christian Dina, S. Gabriel, Jochen Spranger, James S. Pankow, M. Kloppenburg, Penninx Bwjh., Torben Hansen, Josh Smith, Jennie Hui, Gordon H. Williams, Mark Seielstad, Ingrid B. Borecki, Weihua Zhang, Peter P. Pramstaller, Stephen J. Sharp, Neil R. Robertson, Zee Ryl., Mike Sampson, Angela Silveira, C.M. van Duijn, Anders Hamsten, Peter Shrader, Denis Rybin, Chen Y-Di., Gunnar Sigurdsson, Michael Stumvoll, Russel Tracy, Mark O. Goodarzi, Göran Hallmans, Michael R. Erdos, Valeriya Lyssenko, Juha Saharinen, Sven Bergmann, Jeffrey R. O'Connell, Debbie A Lawlor, Thomas Meitinger, Yvonne Böttcher, Jérôme Delplanque, Sarah G. Buxbaum, Silvia Naitza, Shah Ebrahim, Graham A. Hitman, Angelo Scuteri, Aroon D. Hingorani, Heribert Schunkert, François Pattou, Claudia Lamina, A L Elliott, Sekar Kathiresan, Dawn M. Waterworth, Jennifer A. Brody, Thomas Quertermous, Leena Peltonen, Josephine M. Egan, Daniel J. Rader, J F Peden, Yarnell Jwg., Daniel S. Pearson, Pfeiffer Afh., P S Chines, N Vogelzangs, Susan Redline, Alka M. Kanaya, T B Harris, J. V. van Vliet-Ostaptchouk, Ghislain Rocheleau, Rune R. Frants, Olga D. Carlson, James G. Wilson, Melissa Garcia, Ong Rt-H., Mark J. Caulfield, Tanya M. Teslovich, Loo B-M., Beatrice Knight, Andreas Ziegler, Claudia Langenberg, Yoon Shin Cho, Paul M. Ridker, Mark J. Rieder, Praveen Sethupathy, Bert Bravenboer, J. Viikari, Matt Neville, Ioannis M. Stylianou, Andrew Walley, Jarvelin M-R., Jarred B. McAteer, Ronald M. Krauss, Augustine Kong, Oluf Pedersen, Mark J. Daly, Andrew P. Morris, Anna F. Dominiczak, Stéphane Cauchi, Michael Boehnke, Christopher J. O'Donnell, Barbara Thorand, Peter M. Nilsson, Aaron Isaacs, Deborah A. Nickerson, Roza Blagieva, Mary F. Feitosa, Nicholas J. Wareham, Robert Roberts, J S Kooner, K W van Dijk, Tiinamaija Tuomi, Paul Scheet, Lynda M. Rose, Albert V. Smith, Rafn Benediktsson, Chiara Sabatti, Candace Guiducci, Lee M. Kaplan, Aki S. Havulinna, Toby Johnson, Samuli Ripatti, Erik Ingelsson, Mario A. Morken, Carl G. P. Platou, Anke Tönjes, Qi Sun, Narisu Narisu, S J Bumpstead, Jose M. Ordovas, Alan B. Feranil, L Groop, P Chines, Sara M. Willems, Perry Jrb., Matthew A. Allison, Jan Scott, Cécile Lecoeur, Kastelein Jjp., Herman A. Taylor, Anyuan Cao, Christopher J. Groves, Lincoln D. Stein, Laura J. Scott, John Beilby, Kristin G. Ardlie, Christopher S. Franklin, Yoav Ben-Shlomo, B M Shields, N J Timpson, Marco Orrù, Amélie Bonnefond, Kiran Musunuru, Murielle Bochud, Udo Seedorf, Yongmei Liu, Guillaume Lettre, Lee J-Y., Alan R. Shuldiner, Ryan P. Welch, David J. Hunter, John Whitfield, Klaus Strassburger, Khaw K-T., Hartikainen A-L., Gunnar Sigurðsson, Lu Qi, Richard N. Bergman, G M Lathrop, Sigrid W. Fouchier, T van Herpt, David S. Siscovick, Igor Rudan, Richard M. Watanabe, Themistocles L. Assimes, Nicholas G. Martin, Ozren Polasek, Dhiraj Varma, K Kim, Oliver Hofmann, Nicholas D. Hastie, S Bumpstead, Jose C. Florez, Fernando Rivadeneira, Katharine R. Owen, Braxton D. Mitchell, Alisa K. Manning, Abbas Dehghan, Bruce Bartholow Duncan, Cisca Wijmenga, Timo T. Valle, Jaakko Kaprio, Mika Kivimäki, B Shields, Laila Simpson, Tim D. Spector, Paul W. Franks, Guangju Zhai, María Teresa Martínez-Larrad, Janssens Acjw., Kim L. Ward, Inês Barroso, Xiuqing Guo, Rosa Maria Roccasecca, Zari Dastani, Reijo Laaksonen, Wilmar Igl, Vincent Mooser, Niels Grarup, Cornelia Huth, Christian Gieger, Fabio Marroni, Jaakko Tuomilehto, Doney Asf., Andrew C. Edmondson, Christian Fuchsberger, Meena Kumari, David M. Nathan, Reedik Mägi, Solomon K. Musani, U de Faire, Knut Borch-Johnsen, Masahiro Koseki, Giuseppe Paolisso, Norman Klopp, Caroline S. Fox, Nelson B. Freimer, Mika Kähönen, Peter Henneman, Diana Zelenika, K Willems-Vandijk, Steven A. McCarroll, Paul Elliott, Wichmann H-E., J. C. Bis, Nita G. Forouhi, Antti Jula, Witteman Jcm., Fredrik Karpe, Joseph Hung, Antje Fischer-Rosinsky, Eric J. Brunner, Elena Gonzalez, Soumya Raychaudhuri, Jian'an Luan, Josée Dupuis, Joshua C. Randall, Taesung Park, Francis S. Collins, Lori L. Bonnycastle, Andrew A. Hicks, Peter Kovacs, Thomas Illig, Maja Barbalić, David Couper, Jaspal S. Kooner, Damien C. Croteau-Chonka, Gavin Lucas, P J Wagner, Young-Jin Kim, Yurii S. Aulchenko, Aurelian Bidulescu, Ingrid Meulenbelt, Pilar Galan, Iris M. Heid, Michael N. Weedon, Serena Sanna, Sarah H. Wild, Hivert M-F., Patricia B. Munroe, Johan G. Eriksson, Teresa Ferreira, Robert A. Scott, A. Sandbaek, Kenneth Rice, Veronique Vitart, Xin Yuan, Leslie A. Lange, Hilma Holm, Jorge R. Kizer, Timothy M. Frayling, Marika Kaakinen, Liu C-T., Petersen A-K., Peter Schwarz, G B Walters, Palmer Cna., Jean Tichet, Bernhard Paulweber, Ying Wu, Alyson Hall, Christopher T. Johansen, David Masson, Martin Ladouceur, Christie M. Ballantyne, Tai E-S., Robert Luben, Guillaume Charpentier, Angela Döring, Philip J. Barter, Ruth McPherson, Benjamin F. Voight, Wolfgang Rathmann, Mark Walker, Markus Perola, M. A. Province, Veikko Salomaa, James B. Meigs, George Davey Smith, Robert Clarke, Gerard Waeber, Stefania Bandinelli, Sally L. Ricketts, Kaisa Silander, Loos Rjf., Amanda J. Bennett, John C. Chambers, Marilyn C. Cornelis, L A Cupples, Andrew T. Hattersley, M Sandhu, Marju Orho-Melander, C M van Duijn, Olli T. Raitakari, David Meyre, Ida Surakka, Jouke-Jan Hottenga, Uh H-W., Kari Stefansson, David Melzer, P E Slagboom, Kristian Midthjell, Robert K. Semple, James P. Pirruccello, Aloysius G Lieverse, Åsa Johansson, Michael Roden, Felicity Payne, Eric J.G. Sijbrands, N P Burtt, David R. Hillman, Michael Marmot, Todd Green, Eric E. Schadt, Sijbrands Ejg., Tien Yin Wong, Coin Ljm., K B Boström, Olov Rolandsson, A D Morris, David Altshuler, Harald Grallert, L C Groop, Alan F. Wright, Karen Kapur, Xueling Sim, Philippe Froguel, K O Kyvik, T. Lauritzen, Linda S. Adair, Yavuz Ariyurek, Talin Haritunians, Toshiko Tanaka, Albert Hofman, MariaGrazia Franzosi, Nicholas L. Smith, Laura Crisponi, Andrew B. Singleton, A Uitterlinden, Bo Isomaa, Y A Kesaniemi, Anne U. Jackson, Christa Meisinger, Holly E. Syddall, Dorret I. Boomsma, Harry Campbell, Gonçalo R. Abecasis, Lyudmyla Kedenko, Christine Cavalcanti-Proença, G Crawford, Scott M. Grundy, Johnson Prv., Nuotio M-L., I Chen, J.H. Smit, Anuj Goel, M Li, David P. Strachan, Kenechi Ejebe, Beverley Balkau, Neelam Hassanali, Kristian Hveem, Pierre Meneton, R. Gwilliam, A J Swift, Caroline Hayward, J. Graessler, Carina Zabena, B. St Pourcain, Michel Marre, Margot Haun, Lyytikäinen L-P., Ben A. Oostra, Stefan Coassin, M. van Hoek, Nigel W. Rayner, John R. Thompson, Kurt Lohman, Ulla Sovio, Unnur Thorsteinsdottir, Naveed Sattar, Lyle J. Palmer, Ulf Gyllensten, A Elliott, Muredach P. Reilly, A Swift, Luigi Ferrucci, Syvänen A-C., Simon C. Potter, T.W. van Haeften, G Wu, Stefan Böhringer, Grant W. Montgomery, Edward G. Lakatta, Serkalem Demissie, Alex S. F. Doney, Najaf Amin, Lenore J. Launer, Hugh Watkins, Johanna Kuusisto, Lars Lind, Stefan R. Bornstein, Laura J. Rasmussen-Torvik, Terho Lehtimäki, Guillaume Paré, Sophie Visvikis-Siest, S C Heath, David Schlessinger, Juha Sinisalo, Kao Whl., Mark E. Cooper, Kati Kristiansson, Thomas W. Winkler, Thomas Sparsø, Laura J. McCulloch, Taina K. Lajunen, Alex N. Parker, Nabila Bouatia-Naji, Markku S. Nieminen, Peter Vollenweider, Wendy L. McArdle, G K Hovingh, Thomas A. Buchanan, Avan Aihie Sayer, M C Zillikens, Jing Hua Zhao, Naomi Hammond, Vilmundur Gudnason, Björn Zethelius, Panos Deloukas, Jacqueline C. M. Witteman, Eric Boerwinkle, Manuel Serrano-Ríos, Anna L. Gloyn, Katherine S. Elliott, A C Fedson, Torben Jørgensen, Nicole Soranzo, Heather M. Stringham, Bruce M. Psaty, A G Uitterlinden, Stavroula Kanoni, Christian Hengstenberg, Yun Li, Olle Melander, Alan R. Tall, Manuela Uda, Magnusson Pke., Christopher W. Kuzawa, V Mooser, R. M. van Dam, Jerome I. Rotter, Greenwood Cmt., Cyrus Cooper, Pau Navarro, Min Jin Go, Nancy L. Pedersen, Serge Hercberg, Bernhard O. Boehm, Eleanor Wheeler, Epidemiology, Medical Microbiology & Infectious Diseases, Clinical Genetics, Dastani, Z, Hivert, Mf, Timpson, N, Perry, Jr, Yuan, X, Scott, Ra, Henneman, P, Heid, Im, Kizer, Jr, Lyytikäinen, Lp, Fuchsberger, C, Tanaka, T, Morris, Ap, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, J, Uh, Hw, Wu, Y, Bidulescu, A, Rasmussen Torvik, Lj, Greenwood, Cm, Ladouceur, M, Grimsby, J, Manning, Ak, Liu, Ct, Kooner, J, Mooser, Ve, Vollenweider, P, Kapur, Ka, Chambers, J, Wareham, Nj, Langenberg, C, Frants, R, Willems Vandijk, K, Oostra, Ba, Willems, Sm, Lamina, C, Winkler, Tw, Psaty, Bm, Tracy, Rp, Brody, J, Chen, I, Viikari, J, Kähönen, M, Pramstaller, Pp, Evans, Dm, St Pourcain, B, Sattar, N, Wood, Ar, Bandinelli, S, Carlson, Od, Egan, Jm, Böhringer, S, van Heemst, D, Kedenko, L, Kristiansson, K, Nuotio, Ml, Loo, Bm, Harris, T, Garcia, M, Kanaya, A, Haun, M, Klopp, N, Wichmann, He, Deloukas, P, Katsareli, E, Couper, Dj, Duncan, Bb, Kloppenburg, M, Adair, L, Borja, Jb, DIAGRAM+, Consortium, Magic, Consortium, Glgc, Investigator, Muther, Consortium, Wilson, Jg, Musani, S, Guo, X, Johnson, T, Semple, R, Teslovich, Tm, Allison, Ma, Redline, S, Buxbaum, Sg, Mohlke, Kl, Meulenbelt, I, Ballantyne, Cm, Dedoussis, Gv, Hu, Fb, Liu, Y, Paulweber, B, Spector, Td, Slagboom, Pe, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, Jc, Salomaa, V, Eriksson, Jg, Frayling, Tm, Hicks, Aa, Lehtimäki, T, Smith, Gd, Siscovick, D, Kronenberg, F, van Duijn, C, Loos, Rj, Waterworth, Dm, Meigs, Jb, Dupuis, J, Richards, Jb, Voight, Bf, Scott, Lj, Steinthorsdottir, V, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Morris, Ad, Palmer, Cn, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Pedersen, O, Barroso, I, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Elliott, P, Rybin, D, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Lajunen, T, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Diagram, Consortium, Giant, Consortium, Global B., Pgen Consortium, Borecki, Ib, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Serrano Ríos, M, Lind, L, Palmer, Lj, Hu FB, 1st, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Procardis, Consortium, Buchanan, Ta, Valle, Tt, Rotter, Ji, Penninx, Bw, Boomsma, Di, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Peltonen, L, Mooser, V, Magic, Investigator, Glgc, Consortium, Musunuru, K, Smith, Av, Edmondson, Ac, Stylianou, Im, Koseki, M, Pirruccello, Jp, Chasman, Di, Johansen, Ct, Fouchier, Sw, Peloso, Gm, Barbalic, M, Ricketts, Sl, Bis, Jc, Feitosa, Mf, Orho Melander, M, Melander, O, Li, X, Cho, Y, Go, Mj, Kim, Yj, Lee, Jy, Park, T, Kim, K, Sim, X, Ong, Rt, Croteau Chonka, Dc, Lange, La, Smith, Jd, Ziegler, A, Zhang, W, Zee, Ry, Whitfield, Jb, Thompson, Jr, Surakka, I, Smit, Jh, Sinisalo, J, Scott, J, Saharinen, J, Sabatti, C, Rose, Lm, Roberts, R, Rieder, M, Parker, An, Pare, G, O'Donnell, Cj, Nieminen, M, Nickerson, Da, Montgomery, Gw, Mcardle, W, Masson, D, Martin, Ng, Marroni, F, Lucas, G, Luben, R, Lokki, Ml, Lettre, G, Launer, Lj, Lakatta, Eg, Laaksonen, R, König, Ir, Khaw, Kt, Kaplan, Lm, Johansson, Å, Janssens, Ac, Igl, W, Hovingh, Gk, Hengstenberg, C, Havulinna, A, Hastie, Nd, Harris, Tb, Haritunians, T, Hall, A, Groop, Lc, Gonzalez, E, Freimer, Nb, Erdmann, J, Ejebe, Kg, Döring, A, Dominiczak, Af, Demissie, S, de Faire, U, Caulfield, Mj, Boekholdt, Sm, Assimes, Tl, Quertermous, T, Seielstad, M, Wong, Ty, Tai, E, Feranil, Ab, Kuzawa, Cw, Taylor HA, Jr, Gabriel, Sb, Holm, H, Gudnason, V, Krauss, Rm, Ordovas, Jm, Munroe, Pb, Tall, Ar, Hegele, Ra, Kastelein, Jj, Schadt, Ee, Strachan, Dp, Reilly, Mp, Samani, Nj, Schunkert, H, Cupples, La, Ridker, Pm, Rader, Dj, Kathiresan, S., Medical Research Council (MRC), Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Semple, Robert [0000-0001-6539-3069], Griffin, Simon [0000-0002-2157-4797], Barroso, Ines [0000-0001-5800-4520], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Zhao, Jing Hua [0000-0003-4930-3582], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Sandhu, Manjinder [0000-0002-2725-142X], Apollo - University of Cambridge Repository, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Other departments, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Lääketieteen yksikkö - School of Medicine, University of Tampere, Institute for Molecular Medicine Finland, Hjelt Institute (-2014), Clinicum, Department of General Practice and Primary Health Care, Department of Public Health, Haartman Institute (-2014), Transplantation Laboratory, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., and O'Leary, DH.
Subjects: Netherlands Twin Register (NTR), Male, Insulin Resistance/genetics, VARIANTS, 0302 clinical medicine, POPULATION, African Americans, blood/genetics, 0303 health sciences, education.field_of_study, Adiponectin/blood, Adiponectin/genetics, Asian Continental Ancestry Group, Cholesterol, HDL/genetics, Diabetes Mellitus, Type 2/genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Global B Pgen Consortium, MAGIC investigators, 3. Good health, Cholesterol, Medicine, Adiponectin, Type 2, medicine.medical_specialty, HDL, Biolääketieteet - Biomedicine, Single-nucleotide polymorphism, DIAGRAM Consortium, White People, Molecular Genetics, GLGC Consortium, 03 medical and health sciences, Asian People, SDG 3 - Good Health and Well-being, GIANT Consortium, Diabetes Mellitus, Genetics, DIAGRAM+ Consortium, GENOME-WIDE ASSOCIATION, Polymorphism, education, Biology, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 0604 Genetics, Science & Technology, GLGC Investigators, nutritional and metabolic diseases, ta3121, medicine.disease, Obesity, Black or African American, blood/genetics, African Americans, Asian Continental Ancestry Group, Cholesterol, genetics, Diabetes Mellitus, genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, genetics, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio, Endocrinology, Diabetes Mellitus, Type 2, Developmental Biology, Type 2/genetics, Cancer Research, Type 2 diabetes, QH426-470, 030204 cardiovascular system & hematology, LIPID CONCENTRATIONS, GENETICS & HEREDITY, Genetics (clinical), RISK, 2. Zero hunger, INSULIN-RESISTANCE, Glucose tolerance test, medicine.diagnostic_test, MAGIC Consortium, Single Nucleotide, ADIPOSE-TISSUE, CORONARY-ARTERY-DISEASE, Life Sciences & Biomedicine, Research Article, Clinical Research Design, GENETIC-BASIS, Population, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, ddc:610, 030304 developmental biology, RECEPTOR, Cholesterol, HDL, Human Genetics, HDL/genetics, 3121 General medicine, internal medicine and other clinical medicine, MuTHER Consortium, 3111 Biomedicine, Procardis Consortium, Insulin Resistance
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p, Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.
Published: 2012

39. Calcium-permeable AMPA receptors govern PV neuron feature selectivity.

Author: Hong I, Kim J, Hainmueller T, Kim DW, Keijser J, Johnson RC, Park SH, Limjunyawong N, Yang Z, Cheon D, Hwang T, Agarwal A, Cholvin T, Krienen FM, McCarroll SA, Dong X, Leopold DA, Blackshaw S, Sprekeler H, Bergles DE, Bartos M, Brown SP, and Huganir RL
Abstract: The brain helps us survive by forming internal representations of the external world 1,2 . Excitatory cortical neurons are often precisely tuned to specific external stimuli 3,4 . However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective 5 . PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) 6,7 . Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit (encoded by GRIA2), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find low expression stoichiometry of GRIA2 mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Manipulations to induce sparse CP-AMPAR expression demonstrated that this increase was cell-autonomous and could occur with changes beyond development. Notably, excitatory-PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, which suggested that the selectivity of PV interneurons can be altered without markedly changing connectivity. In Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a new role of CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons and implicate a conserved molecular mechanism that distinguishes this cell type in the neocortex., (© 2024. The Author(s).)
Published: 2024
Full Text: View/download PDF

40. Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders.

Author: Datta D, Yang S, Joyce MKP, Woo E, McCarroll SA, Gonzalez-Burgos G, Perone I, Uchendu S, Ling E, Goldman M, Berretta S, Murray J, Morozov Y, Arellano J, Duque A, Rakic P, O'Dell R, van Dyck CH, Lewis DA, Wang M, Krienen FM, and Arnsten AFT
Subjects: Humans, Animals, Male, Cognition Disorders physiopathology, Cognition Disorders genetics, Prefrontal Cortex metabolism, Prefrontal Cortex physiopathology, Dorsolateral Prefrontal Cortex physiology, Macaca mulatta, Memory, Short-Term physiology, Female, Transcriptome, Calcium Channels, L-Type genetics, Calcium Channels, L-Type metabolism, Pyramidal Cells physiology, Pyramidal Cells metabolism
Abstract: Importance: The risk of mental disorders is consistently associated with variants in CACNA1C (L-type calcium channel Cav1.2) but it is not known why these channels are critical to cognition, and whether they affect the layer III pyramidal cells in the dorsolateral prefrontal cortex that are especially vulnerable in cognitive disorders., Objective: To examine the molecular mechanisms expressed in layer III pyramidal cells in primate dorsolateral prefrontal cortices., Design, Setting, and Participants: The design included transcriptomic analyses from human and macaque dorsolateral prefrontal cortex, and connectivity, protein expression, physiology, and cognitive behavior in macaques. The research was performed in academic laboratories at Yale, Harvard, Princeton, and the University of Pittsburgh. As dorsolateral prefrontal cortex only exists in primates, the work evaluated humans and macaques., Main Outcomes and Measures: Outcome measures included transcriptomic signatures of human and macaque pyramidal cells, protein expression and interactions in layer III macaque pyramidal cells using light and electron microscopy, changes in neuronal firing during spatial working memory, and working memory performance following pharmacological treatments., Results: Layer III pyramidal cells in dorsolateral prefrontal cortex coexpress a constellation of calcium-related proteins, delineated by CALB1 (calbindin), and high levels of CACNA1C (Cav1.2), GRIN2B (NMDA receptor GluN2B), and KCNN3 (SK3 potassium channel), concentrated in dendritic spines near the calcium-storing smooth endoplasmic reticulum. L-type calcium channels influenced neuronal firing needed for working memory, where either blockade or increased drive by β1-adrenoceptors, reduced neuronal firing by a mean (SD) 37.3% (5.5%) or 40% (6.3%), respectively, the latter via SK potassium channel opening. An L-type calcium channel blocker or β1-adrenoceptor antagonist protected working memory from stress., Conclusions and Relevance: The layer III pyramidal cells in the dorsolateral prefrontal cortex especially vulnerable in cognitive disorders differentially express calbindin and a constellation of calcium-related proteins including L-type calcium channels Cav1.2 (CACNA1C), GluN2B-NMDA receptors (GRIN2B), and SK3 potassium channels (KCNN3), which influence memory-related neuronal firing. The finding that either inadequate or excessive L-type calcium channel activation reduced neuronal firing explains why either loss- or gain-of-function variants in CACNA1C were associated with increased risk of cognitive disorders. The selective expression of calbindin in these pyramidal cells highlights the importance of regulatory mechanisms in neurons with high calcium signaling, consistent with Alzheimer tau pathology emerging when calbindin is lost with age and/or inflammation.
Published: 2024
Full Text: View/download PDF

41. A sequence of SVA retrotransposon insertions in ASIP shaped human pigmentation.

Author: Kamitaki N, Hujoel MLA, Mukamel RE, Gebara E, McCarroll SA, and Loh PR
Subjects: Humans, Mutagenesis, Insertional, Alleles, Skin Neoplasms genetics, Genome, Human, Introns genetics, Retroelements genetics, Agouti Signaling Protein genetics, Skin Pigmentation genetics
Abstract: Retrotransposons comprise about 45% of the human genome 1 , but their contributions to human trait variation and evolution are only beginning to be explored 2,3 . Here, we find that a sequence of SVA retrotransposon insertions in an early intron of the ASIP (agouti signaling protein) gene has probably shaped human pigmentation several times. In the UK Biobank (n = 169,641), a recent 3.3-kb SVA insertion polymorphism associated strongly with lighter skin pigmentation (0.22 [0.21-0.23] s.d.; P = 2.8 × 10 -351 ) and increased skin cancer risk (odds ratio = 1.23 [1.18-1.27]; P = 1.3 × 10 -28 ), appearing to underlie one of the strongest common genetic influences on these phenotypes within European populations 4-6 . ASIP expression in skin displayed the same association pattern, with the SVA insertion allele exhibiting 2.2-fold (1.9-2.6) increased expression. This effect had an unusual apparent mechanism: an earlier, nonpolymorphic, human-specific SVA retrotransposon 3.9 kb upstream appeared to have caused ASIP hypofunction by nonproductive splicing, which the new (polymorphic) SVA insertion largely eliminated. Extended haplotype homozygosity indicated that the insertion allele has risen to allele frequencies up to 11% in European populations over the past several thousand years. These results indicate that a sequence of retrotransposon insertions contributed to a species-wide increase, then a local decrease, of human pigmentation., (© 2024. The Author(s).)
Published: 2024
Full Text: View/download PDF

42. Transcriptome-wide characterization of genetic perturbations.

Author: Nadig A, Replogle JM, Pogson AN, McCarroll SA, Weissman JS, Robinson EB, and O'Connor LJ
Abstract: Single cell CRISPR screens such as Perturb-seq enable transcriptomic profiling of genetic perturbations at scale. However, the data produced by these screens are often noisy due to cost and technical constraints, limiting power to detect true effects with conventional differential expression analyses. Here, we introduce TRanscriptome-wide Analysis of Differential Expression (TRADE), a statistical framework which estimates the transcriptome-wide distribution of true differential expression effects from noisy gene-level measurements. Within TRADE, we derive multiple novel, interpretable statistical metrics, including the "transcriptome-wide impact", an estimator of the overall transcriptional effect of a perturbation which is stable across sampling depths. We analyze new and published large-scale Perturb-seq datasets to show that many true transcriptional effects are not statistically significant, but detectable in aggregate with TRADE. In a genome-scale Perturb-seq screen, we find that a typical gene perturbation affects an estimated 45 genes, whereas a typical essential gene perturbation affects over 500 genes. An advantage of our approach is its ability to compare the transcriptomic effects of genetic perturbations across contexts and dosages despite differences in power. We use this ability to identify perturbations with cell-type dependent effects and to find examples of perturbations where transcriptional responses are not only larger in magnitude, but also qualitatively different, as a function of dosage. Lastly, we expand our analysis to case/control comparison of gene expression for neuropsychiatric conditions, finding that transcriptomic effect correlations are greater than genetic correlations for these diagnoses. TRADE lays an analytic foundation for the systematic comparison of genetic perturbation atlases, as well as differential expression experiments more broadly., Competing Interests: Declaration of Interests J.S.W. declares outside interest in 5 AM Venture, Amgen, Chroma Medicine, KSQ Therapeutics, Maze Therapeutics, Tenaya Therapeutics, Tessera Therapeutics, Ziada Therapeutics and Third Rock Ventures. J. M. R. consults for Third Rock Ventures and Maze Therapeutics, and is a consultant for and equity holder in Waypoint Bio.
Published: 2024
Full Text: View/download PDF

43. Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS.

Author: Limone F, Mordes DA, Couto A, Joseph BJ, Mitchell JM, Therrien M, Ghosh SD, Meyer D, Zhang Y, Goldman M, Bortolin L, Cobos I, Stevens B, McCarroll SA, Kadiu I, Burberry A, Pietiläinen O, and Eggan K
Subjects: Humans, Risk Factors, Microglia metabolism, Microglia pathology, Cell Nucleus metabolism, Cell Nucleus genetics, Oligodendroglia metabolism, Oligodendroglia pathology, Male, Single-Cell Analysis, Sequence Analysis, RNA, Female, Middle Aged, Nerve Degeneration genetics, Nerve Degeneration pathology, Nerve Degeneration metabolism, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis pathology, Amyotrophic Lateral Sclerosis metabolism, Neurons metabolism, Neurons pathology
Abstract: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls. In both patients and unaffected individuals, we found significantly higher expression of ALS risk genes in THY1 + ETNs, regardless of diagnosis. In patients, this was accompanied by the induction of genes involved in protein homeostasis and stress responses that were significantly induced in a wide collection of ETNs. Examination of oligodendroglial and microglial nuclei revealed patient-specific downregulation of myelinating genes in oligodendrocytes and upregulation of an endolysosomal reactive state in microglia. Our findings suggest that selective vulnerability of extratelencephalic neurons is partly connected to their intrinsic molecular properties sensitizing them to genetics and mechanisms of degeneration., (© 2024. The Author(s).)
Published: 2024
Full Text: View/download PDF

44. CSMD1 regulates brain complement activity and circuit development.

Author: Baum ML, Wilton DK, Fox RG, Carey A, Hsu YH, Hu R, Jäntti HJ, Fahey JB, Muthukumar AK, Salla N, Crotty W, Scott-Hewitt N, Bien E, Sabatini DA, Lanser TB, Frouin A, Gergits F, Håvik B, Gialeli C, Nacu E, Lage K, Blom AM, Eggan K, McCarroll SA, Johnson MB, and Stevens B
Subjects: Animals, Humans, Mice, Cells, Cultured, Complement C3 metabolism, Complement System Proteins metabolism, Mice, Inbred C57BL, Microglia metabolism, Thalamus metabolism, Brain metabolism, Membrane Proteins metabolism, Membrane Proteins genetics, Mice, Knockout, Neurons metabolism, Synapses metabolism
Abstract: Complement proteins facilitate synaptic elimination during neurodevelopmental pruning, but neural complement regulation is not well understood. CUB and Sushi Multiple Domains 1 (CSMD1) can regulate complement activity in vitro, is expressed in the brain, and is associated with increased schizophrenia risk. Beyond this, little is known about CSMD1 including whether it regulates complement activity in the brain or otherwise plays a role in neurodevelopment. We used biochemical, immunohistochemical, and proteomic techniques to examine the regional, cellular, and subcellular distribution as well as protein interactions of CSMD1 in the brain. To evaluate whether CSMD1 is involved in complement-mediated synapse elimination, we examined Csmd1-knockout mice and CSMD1-knockout human stem cell-derived neurons. We interrogated synapse and circuit development of the mouse visual thalamus, a process that involves complement pathway activity. We also quantified complement deposition on synapses in mouse visual thalamus and on cultured human neurons. Finally, we assessed uptake of synaptosomes by cultured microglia. We found that CSMD1 is present at synapses and interacts with complement proteins in the brain. Mice lacking Csmd1 displayed increased levels of complement component C3, an increased colocalization of C3 with presynaptic terminals, fewer retinogeniculate synapses, and aberrant segregation of eye-specific retinal inputs to the visual thalamus during the critical period of complement-dependent refinement of this circuit. Loss of CSMD1 in vivo enhanced synaptosome engulfment by microglia in vitro, and this effect was dependent on activity of the microglial complement receptor, CR3. Finally, human stem cell-derived neurons lacking CSMD1 were more vulnerable to complement deposition. These data suggest that CSMD1 can function as a regulator of complement-mediated synapse elimination in the brain during development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
Full Text: View/download PDF

45. Genetic drivers and cellular selection of female mosaic X chromosome loss.

Author: Liu A, Genovese G, Zhao Y, Pirinen M, Zekavat SM, Kentistou KA, Yang Z, Yu K, Vlasschaert C, Liu X, Brown DW, Hudjashov G, Gorman BR, Dennis J, Zhou W, Momozawa Y, Pyarajan S, Tuzov V, Pajuste FD, Aavikko M, Sipilä TP, Ghazal A, Huang WY, Freedman ND, Song L, Gardner EJ, Sankaran VG, Palotie A, Ollila HM, Tukiainen T, Chanock SJ, Mägi R, Natarajan P, Daly MJ, Bick A, McCarroll SA, Terao C, Loh PR, Ganna A, Perry JRB, and Machiela MJ
Subjects: Adult, Female, Humans, Male, Middle Aged, Alleles, Autoimmune Diseases genetics, Biological Specimen Banks, Chromosome Segregation genetics, Chromosomes, Human, Y genetics, Exome genetics, F-Box Proteins genetics, Genetic Predisposition to Disease genetics, Germ-Line Mutation, Leukemia genetics, Models, Genetic, Multifactorial Inheritance genetics, Mutation, Missense genetics, Aneuploidy, Chromosomes, Human, X genetics, Clone Cells metabolism, Clone Cells pathology, Leukocytes metabolism, Mosaicism
Abstract: Mosaic loss of the X chromosome (mLOX) is the most common clonal somatic alteration in leukocytes of female individuals 1,2 , but little is known about its genetic determinants or phenotypic consequences. Here, to address this, we used data from 883,574 female participants across 8 biobanks; 12% of participants exhibited detectable mLOX in approximately 2% of leukocytes. Female participants with mLOX had an increased risk of myeloid and lymphoid leukaemias. Genetic analyses identified 56 common variants associated with mLOX, implicating genes with roles in chromosomal missegregation, cancer predisposition and autoimmune diseases. Exome-sequence analyses identified rare missense variants in FBXO10 that confer a twofold increased risk of mLOX. Only a small fraction of associations was shared with mosaic Y chromosome loss, suggesting that distinct biological processes drive formation and clonal expansion of sex chromosome missegregation. Allelic shift analyses identified X chromosome alleles that are preferentially retained in mLOX, demonstrating variation at many loci under cellular selection. A polygenic score including 44 allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile. Our results support a model in which germline variants predispose female individuals to acquiring mLOX, with the allelic content of the X chromosome possibly shaping the magnitude of clonal expansion., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2024
Full Text: View/download PDF

46. Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition.

Author: Yang S, Datta D, Krienen FM, Ling E, Woo E, May A, Anderson GM, Galvin VC, Gonzalez-Burgos G, Lewis DA, McCarroll SA, Arnsten AF, and Wang M
Abstract: Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer's disease, and have been correlated with kynurenine inflammatory signaling. Kynurenine is further metabolized to kynurenic acid (KYNA) in brain, where it blocks NMDA and α7-nicotinic receptors (nic-α7Rs). These receptors are essential for neurotransmission in dlPFC, suggesting that KYNA may cause higher cognitive deficits in these disorders. The current study found that KYNA and its synthetic enzyme, KAT II, have greatly expanded expression in primate dlPFC in both glia and neurons. Local application of KYNA onto dlPFC neurons markedly reduced the delay-related firing needed for working memory via actions at NMDA and nic-α7Rs, while inhibition of KAT II enhanced neuronal firing in aged macaques. Systemic administration of agents that reduce KYNA production similarly improved cognitive performance in aged monkeys, suggesting a therapeutic avenue for the treatment of cognitive deficits in neuroinflammatory disorders.
Published: 2024
Full Text: View/download PDF

47. Protein-altering variants at copy number-variable regions influence diverse human phenotypes.

Author: Hujoel MLA, Handsaker RE, Sherman MA, Kamitaki N, Barton AR, Mukamel RE, Terao C, McCarroll SA, and Loh PR
Subjects: Humans, Phenotype, Genetic Association Studies, Exons, DNA Copy Number Variations genetics, Diabetes Mellitus, Type 2 genetics
Abstract: Copy number variants (CNVs) are among the largest genetic variants, yet CNVs have not been effectively ascertained in most genetic association studies. Here we ascertained protein-altering CNVs from UK Biobank whole-exome sequencing data (n = 468,570) using haplotype-informed methods capable of detecting subexonic CNVs and variation within segmental duplications. Incorporating CNVs into analyses of rare variants predicted to cause gene loss of function (LOF) identified 100 associations of predicted LOF variants with 41 quantitative traits. A low-frequency partial deletion of RGL3 exon 6 conferred one of the strongest protective effects of gene LOF on hypertension risk (odds ratio = 0.86 (0.82-0.90)). Protein-coding variation in rapidly evolving gene families within segmental duplications-previously invisible to most analysis methods-generated some of the human genome's largest contributions to variation in type 2 diabetes risk, chronotype and blood cell traits. These results illustrate the potential for new genetic insights from genomic variation that has escaped large-scale analysis to date., (© 2024. The Author(s).)
Published: 2024
Full Text: View/download PDF

48. Modeling interpretable correspondence between cell state and perturbation response with CellCap.

Author: Xu Y, Fleming S, Tegtmeyer M, McCarroll SA, and Babadi M
Abstract: Single-cell transcriptomics, in conjunction with genetic and compound perturbations, offers a robust approach for exploring cellular behaviors in diverse contexts. Such experiments allow uncovering cell-state-specific responses to perturbations, a crucial aspect in unraveling the intricate molecular mechanisms governing cellular behavior and potentially discovering novel regulatory pathways and therapeutic targets. However, prevailing computational methods predominantly focus on predicting average cellular responses, disregarding the inherent response heterogeneity associated with cell state diversity. In this study, we present CellCap, a deep generative model designed for the end-to-end analysis of single-cell perturbation experiments. CellCap employs sparse dictionary learning in a latent space to deconstruct cell-state-specific perturbation responses into a set of transcriptional response programs. These programs are then utilized by each perturbation condition and each cell at varying degrees. The incorporation of specific model design choices, such as dot-product cross-attention between cell states and response programs, along with a linearly-decoded latent space, underlay the interpretation power of CellCap. We evaluate CellCap's model interpretability through multiple simulated scenarios and apply it to two real single-cell perturbation datasets. These datasets feature either heterogeneous cellular populations or a complex experimental setup. Our results demonstrate that CellCap successfully uncovers the relationship between cell state and perturbation response, unveiling novel insights overlooked in previous analyses. The model's interpretability, coupled with its effectiveness in capturing heterogeneous responses, positions CellCap as a valuable tool for advancing our understanding of cellular behaviors in the context of perturbation experiments., Competing Interests: Disclosures The authors declare no competing interests.
Published: 2024
Full Text: View/download PDF

49. A concerted neuron-astrocyte program declines in ageing and schizophrenia.

Author: Ling E, Nemesh J, Goldman M, Kamitaki N, Reed N, Handsaker RE, Genovese G, Vogelgsang JS, Gerges S, Kashin S, Ghosh S, Esposito JM, Morris K, Meyer D, Lutservitz A, Mullally CD, Wysoker A, Spina L, Neumann A, Hogan M, Ichihara K, Berretta S, and McCarroll SA
Subjects: Adult, Aged, Aged, 80 and over, Humans, Middle Aged, Young Adult, Cholesterol metabolism, Cognition, GABAergic Neurons metabolism, Genetic Predisposition to Disease, Glutamine metabolism, Health, Individuality, Neural Inhibition, Neuronal Plasticity, Single-Cell Gene Expression Analysis, Synapses genetics, Synapses metabolism, Synapses pathology, Synaptic Membranes chemistry, Synaptic Membranes metabolism, Aging metabolism, Aging pathology, Astrocytes cytology, Astrocytes metabolism, Astrocytes pathology, Neurons cytology, Neurons metabolism, Neurons pathology, Prefrontal Cortex cytology, Prefrontal Cortex metabolism, Prefrontal Cortex pathology, Schizophrenia genetics, Schizophrenia metabolism, Schizophrenia pathology
Abstract: Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a relationship between people's cortical neurons and cortical astrocytes. We used single-nucleus RNA sequencing to analyse the prefrontal cortex of 191 human donors aged 22-97 years, including healthy individuals and people with schizophrenia. Latent-factor analysis of these data revealed that, in people whose cortical neurons more strongly expressed genes encoding synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the synaptic neuron and astrocyte program (SNAP). In schizophrenia and ageing-two conditions that involve declines in cognitive flexibility and plasticity 1,2 -cells divested from SNAP: astrocytes, glutamatergic (excitatory) neurons and GABAergic (inhibitory) neurons all showed reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy people of similar age, may underlie many aspects of normal human interindividual differences and may be an important point of convergence for multiple kinds of pathophysiology., (© 2024. The Author(s).)
Published: 2024
Full Text: View/download PDF

50. Concerted neuron-astrocyte gene expression declines in aging and schizophrenia.

Author: Ling E, Nemesh J, Goldman M, Kamitaki N, Reed N, Handsaker RE, Genovese G, Vogelgsang JS, Gerges S, Kashin S, Ghosh S, Esposito JM, French K, Meyer D, Lutservitz A, Mullally CD, Wysoker A, Spina L, Neumann A, Hogan M, Ichihara K, Berretta S, and McCarroll SA
Abstract: Human brains vary across people and over time; such variation is not yet understood in cellular terms. Here we describe a striking relationship between people's cortical neurons and cortical astrocytes. We used single-nucleus RNA-seq to analyze the prefrontal cortex of 191 human donors ages 22-97 years, including healthy individuals and persons with schizophrenia. Latent-factor analysis of these data revealed that in persons whose cortical neurons more strongly expressed genes for synaptic components, cortical astrocytes more strongly expressed distinct genes with synaptic functions and genes for synthesizing cholesterol, an astrocyte-supplied component of synaptic membranes. We call this relationship the Synaptic Neuron-and-Astrocyte Program (SNAP). In schizophrenia and aging - two conditions that involve declines in cognitive flexibility and plasticity 1,2 - cells had divested from SNAP: astrocytes, glutamatergic (excitatory) neurons, and GABAergic (inhibitory) neurons all reduced SNAP expression to corresponding degrees. The distinct astrocytic and neuronal components of SNAP both involved genes in which genetic risk factors for schizophrenia were strongly concentrated. SNAP, which varies quantitatively even among healthy persons of similar age, may underlie many aspects of normal human interindividual differences and be an important point of convergence for multiple kinds of pathophysiology., Competing Interests: COMPETING INTERESTS The authors declare no competing interests.
Published: 2024
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

235 results on '"McCarroll SA"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources