Author: "Pankratz, N." - Searchworks@Jio Institute Digital Library Search Results

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263 results on '"Pankratz, N."'

1. Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation

Author: Longchamps, RJ, Yang, SY, Castellani, CA, Shi, W, Lane, J, Grove, ML, Bartz, TM, Sarnowski, C, Liu, C, Burrows, K, Guyatt, AL, Gaunt, TR, Kacprowski, T, Yang, J, De Jager, PL, Yu, L, Bergman, A, Xia, R, Fornage, M, Feitosa, MF, Wojczynski, MK, Kraja, AT, Province, MA, Amin, N, Rivadeneira, F, Tiemeier, H, Uitterlinden, AG, Broer, L, Van Meurs, JBJ, Van Duijn, CM, Raffield, LM, Lange, L, Rich, SS, Lemaitre, RN, Goodarzi, MO, Sitlani, CM, Mak, ACY, Bennett, DA, Rodriguez, S, Murabito, JM, Lunetta, KL, Sotoodehnia, N, Atzmon, G, Ye, K, Barzilai, N, Brody, JA, Psaty, BM, Taylor, KD, Rotter, JI, Boerwinkle, E, Pankratz, N, and Arking, DE
Subjects: Biological Sciences, Genetics, Aging, Cancer, Human Genome, 1.1 Normal biological development and functioning, Underpinning research, Cardiovascular, Generic health relevance, Aged, Cell Proliferation, DNA Copy Number Variations, DNA, Mitochondrial, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Megakaryocytes, Middle Aged, Mitochondria, Nucleotides, Phenotype, Platelet Activation, Polymorphism, Single Nucleotide, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract: Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10-15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10-8) and mtDNA replication (p = 1.2 × 10-7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10-4).
Published: 2022

2. Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.

Author: Yoneyama, S, Yao, J, Guo, X, Fernandez-Rhodes, L, Lim, U, Boston, J, Buzková, P, Carlson, CS, Cheng, I, Cochran, B, Cooper, R, Ehret, G, Fornage, M, Gong, J, Gross, M, Gu, CC, Haessler, J, Haiman, CA, Henderson, B, Hindorff, LA, Houston, D, Irvin, MR, Jackson, R, Kuller, L, Leppert, M, Lewis, CE, Li, R, Le Marchand, L, Matise, TC, Nguyen, K-Dh, Chakravarti, A, Pankow, JS, Pankratz, N, Pooler, L, Ritchie, MD, Bien, SA, Wassel, CL, Chen, Y-DI, Taylor, KD, Allison, M, Rotter, JI, Schreiner, PJ, Schumacher, F, Wilkens, L, Boerwinkle, E, Kooperberg, C, Peters, U, Buyske, S, Graff, M, and North, KE
Subjects: Humans, Genetic Predisposition to Disease, Waist-Hip Ratio, Genotype, Polymorphism, Single Nucleotide, Adult, African Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiposity, Body Fat Distribution, Genetic Variation, Genome-Wide Association Study, Obesity, Abdominal, Polymorphism, Single Nucleotide, Obesity, Abdominal, Endocrinology & Metabolism, Medical and Health Sciences, Education
Abstract: Background/objectivesCentral adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of body mass index (BMI) and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition.Subjects/methodsTo identify the underlying functional genetic determinants of body fat distribution, we conducted an array-wide association meta-analysis among persons of African ancestry across seven studies/consortia participating in the Population Architecture using Genomics and Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine-mapping cardiovascular-associated loci, to explore novel array-wide associations with WC and WHR among 15 945 African descendants using all and sex-stratified groups. We further interrogated 17 known WHR regions for African ancestry-specific variants.ResultsOf the 17 WHR loci, eight single-nucleotide polymorphisms (SNPs) located in four loci were replicated in the sex-combined or sex-stratified meta-analyses. Two of these eight independently associated with WHR after conditioning on the known variant in European descendants (rs12096179 in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the putative functional region was reduced across all four loci but to varying degrees (average 40% drop in number of putative SNPs and 20% drop in genomic region). Similar to previous studies, the significant SNPs in the female-stratified analysis were stronger than the significant SNPs from the sex-combined analysis. No novel associations were detected in the array-wide analyses.ConclusionsOf 17 previously identified loci, four loci replicated in the African ancestry populations of this study. Utilizing different linkage disequilibrium patterns observed between European and African ancestries, we narrowed the suggestive region containing causative variants for all four loci.
Published: 2017

3. Climate Change, Firm Performance, and Investor Surprises

Author: Pankratz, N., Bauer, R., Derwall, J., Pankratz, N., Bauer, R., and Derwall, J.
Abstract: We link records of firm performance, equity analyst forecast errors, and stock returns around companies' earnings announcements to firm-specific measures of heat exposure for more than 17,000 firms in 93 countries from 1995 to 2019. We find that increased exposure to extremely high temperatures reduces firms' revenues and operating income. A one-standard-deviation increase in the number of hot days decreases revenues (operating income) by 0.6% (1.8%) of the average quarterly revenue (operating income). Moreover, we provide evidence that increased heat exposure impacts negatively on firm financial performance relative to analyst predictions and on earnings announcement returns. These findings indicate that capital market participants do not fully anticipate the economic consequences of heat as a first order physical climate risk.
Published: 2023

4. Prediction of venous thromboembolism incidence in the general adult population using two published genetic risk scores

Author: Hong, C.-P., Pankratz, N., Cushman, M., Rosamond, W.D., Lane, J.A., Folsom, A.R., and Tang, W.
Abstract: Introduction Most strategies for prevention of venous thromboembolism focus on preventing recurrent events. Yet, primary prevention might be possible through approaches targeting the whole population or high-risk patients. To inform possible prevention strategies, population-based information on the ability of genetic risk scores to identify risk of incident venous thromboembolism is needed. Materials and methods We used proportional hazards regression to relate two published genetic risk scores (273-variants versus 5-variants) with venous thromboembolism incidence in the Atherosclerosis Risk in Communities Study (ARIC) cohort (n = 11,292), aged 45–64 at baseline, drawn from 4 US communities. Results Over a median of 28 years, ARIC identified 788 incident venous thromboembolism events. Incidence rates rose more than two-fold across quartiles of the 273-variant genetic risk score: 1.7, 2.7, 3.4 and 4.0 per 1,000 person-years. For White participants, age, sex, and ancestry-adjusted hazard ratios (95% confidence intervals) across quartiles were strong [1 (reference), 1.30 (0.99,1.70), 1.85 (1.43,2.40), and 2.58 (2.04,3.28)] but weaker for Black participants [1, 1.05 (0.63,1.75), 1.37 (0.84,2.22), and 1.32 (0.80,2.20)]. The 5-variant genetic risk score showed a less steep gradient, with hazard ratios in Whites of 1, 1.17 (0.89,1.54), 1.48 (1.14,1.92), and 2.18 (1.71,2.79). Models including the 273-variant genetic risk score plus lifestyle and clinical factors had a c-statistic of 0.67. Conclusions In the general population, middle-aged adults in the highest quartile of either genetic risk score studied have approximately two-fold higher risk of an incident venous thromboembolism compared with the lowest quartile. The genetic risk scores show a weaker association with venous thromboembolism for Black people.
Published: 2023
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5. Cross-ancestry investigation of venousc genomic predictors

Author: Thibord, F., Klarin, D., Brody, J.A., Chen, M.H., Levin, M.G., Chasman, D.I., Goode, E.L., Hveem, K., Teder-Laving, M., Martinez-Perez, A., Aissi, D., Daian-Bacq, D., Ito, K., Natarajan, P., Lutsey, P.L., Nadkarni, G.N., Vries, P.S. de, Cuellar-Partida, G., Wolford, B.N., Pattee, J.W., Kooperberg, C., Braekkan, S.K., Li-Gao, R.F., Saut, N., Sept, C., Germain, M., Judy, R.L., Wiggins, K.L., Ko, D., O'Donnell, C.J., Taylor, K.D., Giulianini, F., Andrade, M. de, Nost, T.H., Boland, A., Empana, J.P., Koyama, S., Gilliland, T., R. do, Huffman, J.E., Wang, X., Zhou, W., Soria, J.M., Souto, J.C., Pankratz, N., Haessler, J., Hindberg, K., Rosendaal, F.R., Turman, C., Olaso, R., Kember, R.L., Bartz, T.M., Lynch, J.A., Heckbert, S.R., Armasu, S.M., Brumpton, B., Smadja, D.M., Jouven, X., Komuro, I., Clapham, K.R., Loos, R.J.F., Willer, C.J., Sabater-Lleal, M., Pankow, J.S., Reiner, A.P., Morelli, V.M., Ridker, P.M., Vlieg, A.V., Deleuze, J.F., Kraft, P., Rader, D.J., Lee, K.M., Psaty, B.M., Skogholt, A.H., Emmerich, J., Suchon, P., Rich, S.S., Vy, H.T., Tang, W.H., Jackson, R.D., Hansen, J.B., Morange, P.E., Kabrhel, C., Tregouet, D.A., Damrauer, S.M., Johnson, A.D., and Smith, N.L.
Subjects: meta-analysis, genome-wide association study, venous thromboembolism, genetics, venous thrombosis
Abstract: Background: Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources. Methods: We present new cross-ancestry meta-analyzed GWAS results involving up to 81 669 VTE cases from 30 studies, with replication of novel loci in independent populations and loci characterization through in silico genomic interrogations. Results: In our genetic discovery effort that included 55 330 participants with VTE (47 822 European, 6320 African, and 1188 Hispanic ancestry), we identified 48 novel associations, of which 34 were replicated after correction for multiple testing. In our combined discovery-replication analysis (81 669 VTE participants) and ancestry-stratified meta-analyses (European, African, and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. A genetic risk score of the significantly associated loci in Europeans identified a 6-fold increase in risk for those in the top 1% of scores compared with those with average scores. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein quantitative-trait locus Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 GWAS loci provided insights to biological pathways contributing to VTE, with some loci contributing to VTE through well-characterized coagulation pathways and others providing new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis. Conclusions: Our cross-ancestry GWAS meta-analyses identified new loci associated with VTE. These findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.
Published: 2022

6. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
Published: 2022

7. Multi-phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author: Temprano-Sagrera, G, Sitlani, CM, Bone, WP, Martin-Bornez, M, Voight, BF, Morrison, AC, Damrauer, SM, de Vries, PS, Smith, NL, Sabater-Lleal, M, Krupinksi, J, Dehghan, A, Heath, AS, Reiner, AP, Johnson, A, Richmond, A, Peters, A, van Hylckama Vlieg, A, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O’Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Liu, M, Brown, MR, Conomos, MP, Jhun, MA, Chen, MH, de Maat, MPM, Pankratz, N, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, R, Cox, SR, Trompet, S, Felix, SB, Völker, U, Tang, W, Koenig, W, Jukema, JW, Guo, X, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, de Andrade, M, Brody, JA, Pattee, JW, Haessler, J, Brumpton, BM, Chasman, DI, Suchon, P, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Temprano-Sagrera, G, Sitlani, CM, Bone, WP, Martin-Bornez, M, Voight, BF, Morrison, AC, Damrauer, SM, de Vries, PS, Smith, NL, Sabater-Lleal, M, Krupinksi, J, Dehghan, A, Heath, AS, Reiner, AP, Johnson, A, Richmond, A, Peters, A, van Hylckama Vlieg, A, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O’Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Liu, M, Brown, MR, Conomos, MP, Jhun, MA, Chen, MH, de Maat, MPM, Pankratz, N, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, R, Cox, SR, Trompet, S, Felix, SB, Völker, U, Tang, W, Koenig, W, Jukema, JW, Guo, X, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, de Andrade, M, Brody, JA, Pattee, JW, Haessler, J, Brumpton, BM, Chasman, DI, Suchon, P, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, and Armasu, SM
Abstract: Background: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes. Objectives: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events. Methods: Summary statistics from genome wide-association studies (GWAS) from seven hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and three major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 × 10−9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27). Results: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes. Conclusions: The discovery of four novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.
Published: 2022

8. Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation

Author: Longchamps, R. J., Yang, S. Y., Castellani, C. A., Shi, W., Lane, J., Grove, M. L., Bartz, T. M., Sarnowski, C., Liu, C., Burrows, K., Guyatt, A. L., Gaunt, T. R., Kacprowski, T., Yang, J., De Jager, P. L., Yu, L., Bergman, A., Xia, R., Fornage, M., Feitosa, M. F., Wojczynski, M. K., Kraja, A. T., Province, M. A., Amin, N., Rivadeneira, F., Tiemeier, H., Uitterlinden, A. G., Broer, L., Van Meurs, J. B.J., Van Duijn, C. M., Raffield, L. M., Lange, L., Rich, S. S., Lemaitre, R. N., Goodarzi, M. O., Sitlani, C. M., Mak, A.C.Y., Bennett, D. A., Rodriguez, S., Murabito, J. M., Lunetta, K. L., Sotoodehnia, N., Atzmon, G., Ye, K., Barzilai, N., Brody, J. A., Psaty, B. M., Taylor, K. D., Rotter, J. I., Boerwinkle, E., Pankratz, N., Arking, D. E., Longchamps, R. J., Yang, S. Y., Castellani, C. A., Shi, W., Lane, J., Grove, M. L., Bartz, T. M., Sarnowski, C., Liu, C., Burrows, K., Guyatt, A. L., Gaunt, T. R., Kacprowski, T., Yang, J., De Jager, P. L., Yu, L., Bergman, A., Xia, R., Fornage, M., Feitosa, M. F., Wojczynski, M. K., Kraja, A. T., Province, M. A., Amin, N., Rivadeneira, F., Tiemeier, H., Uitterlinden, A. G., Broer, L., Van Meurs, J. B.J., Van Duijn, C. M., Raffield, L. M., Lange, L., Rich, S. S., Lemaitre, R. N., Goodarzi, M. O., Sitlani, C. M., Mak, A.C.Y., Bennett, D. A., Rodriguez, S., Murabito, J. M., Lunetta, K. L., Sotoodehnia, N., Atzmon, G., Ye, K., Barzilai, N., Brody, J. A., Psaty, B. M., Taylor, K. D., Rotter, J. I., Boerwinkle, E., Pankratz, N., and Arking, D. E.
Abstract: Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10–15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10–8) and mtDNA replication (p = 1.2 × 10–7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10–4).
Published: 2022

9. Elucidating mechanisms of genetic cross-disease associations at the PROCR vascular disease locus (vol 13, 1222, 2022)

Author: Stacey, D, Chen, LY, Stanczyk, PJ, Howson, JMM, Mason, AM, Burgess, S, MacDonald, S, Langdown, J, McKinney, H, Downes, K, Farahi, N, Peters, JE, Basu, S, Pankow, JS, Tang, WH, Pankratz, N, Sabater-Lleal, M, de Vries, PS, Smith, NL, Dehghan, A, Heath, AS, Morrison, AC, Reiner, AP, Johnson, A, Richmond, A, Peters, A, Vlieg, AV, McKnight, B, Psaty, BM, Hayward, C, Ward-Caviness, C, O'Donnell, C, Chasman, D, Strachan, DP, Tregouet, DA, Mook-Kanamori, D, Gill, D, Thibord, F, Asselbergs, FW, Leebeek, FWG, Rosendaal, FR, Davies, G, Homuth, G, Temprano, G, Campbell, H, Taylor, HA, Bressler, J, Huffman, JE, Rotter, JI, Yao, J, Wilson, JF, Bis, JC, Hahn, JM, Desch, KC, Wiggins, KL, Raffield, LM, Bielak, LF, Yanek, LR, Kleber, ME, Mueller, M, Kavousi, M, Mangino, M, Conomos, MP, Liu, ML, Brown, MR, Jhun, MA, Chen, MH, de Maat, MPM, Peyser, PA, Elliot, P, Wei, P, Wild, PS, Morange, PE, van der Harst, P, Yang, Q, Le, NQ, Marioni, R, Li, RF, Damrauer, SM, Cox, SR, Trompet, S, Felix, SB, Volker, U, Koenig, W, Jukema, JW, Guo, XQ, Gelinas, AD, Schneider, DJ, Janjic, N, Samani, NJ, Ye, S, Summers, C, Chilvers, ER, Danesh, J, and Paul, DS
Published: 2022

10. Genome-wide analysis of mitochondrial DNA copy number reveals loci implicated in nucleotide metabolism, platelet activation, and megakaryocyte proliferation

Author: Longchamps, R. J., primary, Yang, S. Y., additional, Castellani, C. A., additional, Shi, W., additional, Lane, J., additional, Grove, M. L., additional, Bartz, T. M., additional, Sarnowski, C., additional, Liu, C., additional, Burrows, K., additional, Guyatt, A. L., additional, Gaunt, T. R., additional, Kacprowski, T., additional, Yang, J., additional, De Jager, P. L., additional, Yu, L., additional, Bergman, A., additional, Xia, R., additional, Fornage, M., additional, Feitosa, M. F., additional, Wojczynski, M. K., additional, Kraja, A. T., additional, Province, M. A., additional, Amin, N., additional, Rivadeneira, F., additional, Tiemeier, H., additional, Uitterlinden, A. G., additional, Broer, L., additional, Van Meurs, J. B. J., additional, Van Duijn, C. M., additional, Raffield, L. M., additional, Lange, L., additional, Rich, S. S., additional, Lemaitre, R. N., additional, Goodarzi, M. O., additional, Sitlani, C. M., additional, Mak, A. C. Y., additional, Bennett, D. A., additional, Rodriguez, S., additional, Murabito, J. M., additional, Lunetta, K. L., additional, Sotoodehnia, N., additional, Atzmon, G., additional, Ye, K., additional, Barzilai, N., additional, Brody, J. A., additional, Psaty, B. M., additional, Taylor, K. D., additional, Rotter, J. I., additional, Boerwinkle, E., additional, Pankratz, N., additional, and Arking, D. E., additional
Published: 2021
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11. Allelic Heterogeneity at the CRP Locus Identified by Whole-Genome Sequencing in Multi-ancestry Cohorts

Author: Gaynor, S.M., Lee, S., Lee, J., Yanek, L.R., Correa, A., Metcalf, G.A., Rotter, J.I., TOPMed Inflammation Working Group, Kowalski, M.H., Mohlke, K.L., Kral, B.G., Seo, D., Rockville, MD 20850, United States, Dupuis, J., Cruz, P., Bis, J.C., Tracy, R.P., Lange, L.A., Park, C.J., Comellas, A.P., Larson, M.G., Raffield, L.M., Lin, X., Pankratz, N., Polfus, L.M., Jain, D., Gogarten, S.M., Benjamin, E.J., Muzny, D.M., Kim, R.W., Rockville, MD 20850, United States, Zhong, X., Durda, P., Choi, W.J., Mitchell, B.D., Iyengar, A.K., Zhao, L.P., Bowler, R., Rich, S.S., Reiner, A.P., Ryan, K., Spracklen, C.N., Doddapaneni, H., NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Viaud-Martinez, K.A., Wang, B., Momin, Z., Li, B., Laurie, C., Salimi, S., Cade, B.E., Li, Y., Lewis, J.P., and Auer, P.L.
Subjects: Black People, Medical and Health Sciences, Linkage Disequilibrium, White People, Cohort Studies, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Gene Frequency, Asian People, c-reactive protein, Clinical Research, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Polymorphism, Aetiology, Genetics & Heredity, Whole Genome Sequencing, TOPMed Inflammation Working Group, Human Genome, Single Nucleotide, Biological Sciences, Good Health and Well Being, whole-genome sequencing, Genome-Wide Association Study, Biotechnology
Abstract: Whole-genome sequencing (WGS) can improve assessment of low-frequency and rare variants, particularly in non-European populations that have been underrepresented in existing genomic studies. The genetic determinants of C-reactive protein (CRP), a biomarker of chronic inflammation, have been extensively studied, with existing genome-wide association studies (GWASs) conducted in >200,000 individuals of European ancestry. In order to discover novel loci associated with CRP levels, we examined a multi-ancestry population (n = 23,279) with WGS (∼38× coverage) from the Trans-Omics for Precision Medicine (TOPMed) program. We found evidence for eight distinct associations at the CRP locus, including two variants that have not been identified previously (rs11265259 and rs181704186), both of which are non-coding and more common in individuals of African ancestry (∼10% and ∼1% minor allele frequency, respectively, and rare or monomorphic in 1000 Genomes populations of East Asian, South Asian, and European ancestry). We show that the minor (G) allele of rs181704186 is associated with lower CRP levels and decreased transcriptional activity and protein binding invitro, providing a plausible molecular mechanism for this African ancestry-specific signal. The individuals homozygous for rs181704186-G have a mean CRP level of 0.23mg/L, in contrast to individuals heterozygous for rs181704186 with mean CRP of 2.97mg/L and major allele homozygotes with mean CRP of 4.11mg/L. This study demonstrates the utility of WGS in multi-ethnic populations to drive discovery of complex trait associations of large effect and to identify functional alleles in noncoding regulatory regions.
Published: 2020

12. The Polygenic and Monogenic Basis of Blood Traits and Diseases

Author: Vuckovic, D, Bao, EL, Akbari, P, Lareau, CA, Mousas, A, Jiang, T, Chen, M-H, Raffield, LM, Tardaguila, M, Huffman, JE, Ritchie, SC, Megy, K, Ponstingl, H, Penkett, CJ, Albers, PK, Wigdor, EM, Sakaue, S, Moscati, A, Manansala, R, Lo, KS, Qian, H, Akiyama, M, Bartz, TM, Ben-Shlomo, Y, Beswick, A, Bork-Jensen, J, Bottinger, EP, Brody, JA, van Rooij, FJA, Chitrala, KN, Wilson, PWF, Choquet, H, Danesh, J, Di Angelantonio, E, Dimou, N, Ding, J, Elliott, P, Esko, T, Evans, MK, Felix, SB, Floyd, JS, Broer, L, Grarup, N, Guo, MH, Guo, Q, Greinacher, A, Haessler, J, Hansen, T, Howson, JMM, Huang, W, Jorgenson, E, Kacprowski, T, Kahonen, M, Kamatani, Y, Kanai, M, Karthikeyan, S, Koskeridis, F, Lange, LA, Lehtimaki, T, Linneberg, A, Liu, Y, Lyytikainen, L-P, Manichaikul, A, Matsuda, K, Mohlke, KL, Mononen, N, Murakami, Y, Nadkarni, GN, Nikus, K, Pankratz, N, Pedersen, O, Preuss, M, Psaty, BM, Raitakari, OT, Rich, SS, Rodriguez, BAT, Rosen, JD, Rotter, JI, Schubert, P, Spracklen, CN, Surendran, P, Tang, H, Tardif, J-C, Ghanbari, M, Volker, U, Volzke, H, Watkins, NA, Weiss, S, Cai, N, Kundu, K, Watt, SB, Walter, K, Zonderman, AB, Cho, K, Li, Y, Loos, RJF, Knight, JC, Georges, M, Stegle, O, Evangelou, E, Okada, Y, Roberts, DJ, Inouye, M, Johnson, AD, Auer, PL, Astle, WJ, Reiner, AP, Butterworth, AS, Ouwehand, WH, Lettre, G, Sankaran, VG, Soranzo, N, Vuckovic, D, Bao, EL, Akbari, P, Lareau, CA, Mousas, A, Jiang, T, Chen, M-H, Raffield, LM, Tardaguila, M, Huffman, JE, Ritchie, SC, Megy, K, Ponstingl, H, Penkett, CJ, Albers, PK, Wigdor, EM, Sakaue, S, Moscati, A, Manansala, R, Lo, KS, Qian, H, Akiyama, M, Bartz, TM, Ben-Shlomo, Y, Beswick, A, Bork-Jensen, J, Bottinger, EP, Brody, JA, van Rooij, FJA, Chitrala, KN, Wilson, PWF, Choquet, H, Danesh, J, Di Angelantonio, E, Dimou, N, Ding, J, Elliott, P, Esko, T, Evans, MK, Felix, SB, Floyd, JS, Broer, L, Grarup, N, Guo, MH, Guo, Q, Greinacher, A, Haessler, J, Hansen, T, Howson, JMM, Huang, W, Jorgenson, E, Kacprowski, T, Kahonen, M, Kamatani, Y, Kanai, M, Karthikeyan, S, Koskeridis, F, Lange, LA, Lehtimaki, T, Linneberg, A, Liu, Y, Lyytikainen, L-P, Manichaikul, A, Matsuda, K, Mohlke, KL, Mononen, N, Murakami, Y, Nadkarni, GN, Nikus, K, Pankratz, N, Pedersen, O, Preuss, M, Psaty, BM, Raitakari, OT, Rich, SS, Rodriguez, BAT, Rosen, JD, Rotter, JI, Schubert, P, Spracklen, CN, Surendran, P, Tang, H, Tardif, J-C, Ghanbari, M, Volker, U, Volzke, H, Watkins, NA, Weiss, S, Cai, N, Kundu, K, Watt, SB, Walter, K, Zonderman, AB, Cho, K, Li, Y, Loos, RJF, Knight, JC, Georges, M, Stegle, O, Evangelou, E, Okada, Y, Roberts, DJ, Inouye, M, Johnson, AD, Auer, PL, Astle, WJ, Reiner, AP, Butterworth, AS, Ouwehand, WH, Lettre, G, Sankaran, VG, and Soranzo, N
Abstract: Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Published: 2020

13. Genomic and transcriptomic association studies identify 16 novel susceptibility loci for venous thromboembolism

Author: Lindstrom, S., Wang, L., Smith, E.N., Gordon, W., Vlieg, A.V., Andrade, M. de, Brody, J.A., Pattee, J.W., Haessler, J., Brumpton, B., Chasman, D.I., Suchon, P., Chen, M.H., Turman, C., Germain, M., Wiggins, K.L., MacDonald, J., Braekkan, S.K., Armasu, S.M., Pankratz, N., Jackson, R.D., Nielsen, J.B., Giulianini, F., Puurunen, M.K., Ibrahim, M., Heckbert, S.R., Damrauer, S.M., Natarajan, P., Klarin, D., Vries, P.S. de, Sabater-Lleal, M., Huffman, J.E., Bammler, T.K., Frazer, K.A., McCauley, B.M., Taylor, K., Pankow, J.S., Reiner, A.P., Gabrielsen, M.E., Deleuze, J.F., O'Donnell, C.J., Kim, J., McKnight, B., Kraft, P., Hansen, J.B., Rosendaal, F.R., Heit, J.A., Psaty, B.M., Tang, W.H., Kooperberg, C., Hveem, K., Ridker, P.M., Morange, P.E., Johnson, A.D., Kabrhel, C., Tregouet, D.A., Smith, N.L., Busenkell, E., Judy, R., Lynch, J., Levin, M., Aragam, J.H.K., Chaffin, M., Haas, M., Assimes, T.L., Huang, J., Lee, K.M., Shao, Q., Huang, Y.F., Sun, Y.V., Vujkovic, M., Saleheen, D., Miller, D.R., Reaven, P., DuVall, S., Boden, W., Pyarajan, S., Henke, P., Gaziano, J.M., Concato, J., Rader, D.J., Cho, K., Chang, K.M., Wilson, P.W.F., Tsao, P.S., Kathiresan, S., Obi, A., Million Veteran Program, CHARGE Hemostasis Working Grp, INVENT Consortium, Program in Genetic Epidemiology and Statistical Genetics (PGESG - BOSTON), Harvard School of Public Health, University of Washington [Seattle], The Scripps Translational Science Institute and Scripps Health, Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, University of Minnesota System, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Brigham and Women's Hospital [Boston], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), National Institutes of Health [Bethesda] (NIH), Harvard T.H. Chan School of Public Health, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biorobotics Lab (University of Washington), University of South-Eastern Norway (USN), Department of Health Sciences Research, Ohio State University [Columbus] (OSU), Nutrition, obésité et risque thrombotique (NORT), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Los Angeles Biomedical Research Institute (LA BioMed), University of Augsburg [Augsburg], Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Epidemiology, Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, University of Minnesota [Twin Cities] (UMN), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU), Department of Emergency Medicine, Massachusetts General Hospital [Boston], Universiteit Leiden-Universiteit Leiden, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Augsburg (UNIA), and Universiteit Leiden
Subjects: 0301 basic medicine, Genetics, [SDV]Life Sciences [q-bio], Immunology, Genome-wide association study, Cell Biology, Hematology, 030204 cardiovascular system & hematology, Biology, equipment and supplies, Biochemistry, 3. Good health, Transcriptome, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Mendelian randomization, Expression quantitative trait loci, Gene expression, cardiovascular diseases, Gene, Genetic association, Whole blood
Abstract: Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality. To advance our understanding of the biology contributing to VTE, we conducted a genome-wide association study (GWAS) of VTE and a transcriptome-wide association study (TWAS) based on imputed gene expression from whole blood and liver. We meta-analyzed GWAS data from 18 studies for 30 234 VTE cases and 172 122 controls and assessed the association between 12 923 718 genetic variants and VTE. We generated variant prediction scores of gene expression from whole blood and liver tissue and assessed them for association with VTE. Mendelian randomization analyses were conducted for traits genetically associated with novel VTE loci. We identified 34 independent genetic signals for VTE risk from GWAS meta-analysis, of which 14 are newly reported associations. This included 11 newly associated genetic loci (C1orf198, PLEK, OSMR-AS1, NUGGC/SCARA5, GRK5, MPHOSPH9, ARID4A, PLCG2, SMG6, EIF5A, and STX10) of which 6 replicated, and 3 new independent signals in 3 known genes. Further, TWAS identified 5 additional genetic loci with imputed gene expression levels differing between cases and controls in whole blood (SH2B3, SPSB1, RP11-747H7.3, RP4-737E23.2) and in liver (ERAP1). At some GWAS loci, we found suggestive evidence that the VTE association signal for novel and previously known regions colocalized with expression quantitative trait locus signals. Mendelian randomization analyses suggested that blood traits may contribute to the underlying risk of VTE. To conclude, we identified 16 novel susceptibility loci for VTE; for some loci, the association signals are likely mediated through gene expression of nearby genes.
Published: 2019

14. Use of >100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations

Author: Cai, J., NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Qian, H., Montgomery, C., Kelly, T.N., Cho, M.H., Weiss, S.T., Loos, R.J.F., Johnson, A.D., de Vries, P.S., Li, Y., Becker, L.C., Peralta, J.M., Wiggins, K.L., Bowden, D.W., Lasky-Su, J.A., Buyske, S., Shan, Y., Moon, J.-Y., Jorgenson, E., Cushman, M., Tiwari, H.K., Kooperberg, C., Faraday, N., Tapia, A.L., TOPMed Hematology & Hemostasis Working Group, Thornton, T.A., Choquet, H., Barnes, K.C., Bis, J.C., Hodonsky, C.J., Mathias, R.A., Wang, T., Taylor, K.D., He, J., Kaplan, R., Gupta, N., Lubitz, S.A., Smith, N.L., Daya, M., Rich, S.S., Peyser, P.A., Palmer, N.D., Silverman, E.K., Arnett, D.K., Choi, S.H., Cupples, L. A., Reiner, A.P., Argos, M., Boerwinkle, E., Hou, Z., Auer, P.L., Bien, S.A., Hidalgo, B., Ellinor, P.T., Heckbert, S.R., Gabriel, S., Tracy, R.P., Avery, C., Yanek, L.R., Raffield, L.M., Papanicolaou, G.J., Fornage, M., Z��llner, S., Graff, M., Wilson, J.G., Smith, J.A., Weng, L.-C., Morrison, A.C., Rosen, J.D., Irvin, M.R., North, K.E., Kardia, S.L.R., Pankratz, N., Rotter, J.I., Blangero, J., McHugh, C.P., Jain, D., Kowalski, M.H., and Ganesh, S.K.
Abstract: Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged >100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) < 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11-34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count 86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations.
Published: 2019
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15. A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology

Author: de Vries, PS, Sabater-Lleal, M, Huffman, JE, Marten, J, Song, C, Pankratz, N, Bartz, TM, de Haan, HG, Delgado, GE, Eicher, JD, Martinez-Perez, A, Ward-Caviness, CK, Brody, JA, Chen, MH, de Maat, MPM, Franberg, M, Gill, D, Kleber, ME, Rivadeneira, F, Soria, JM, Tang, WH, Tofler, GH, Uitterlinden, AG, Vlieg, AV, Seshadri, S, Boerwinkle, E, Davies, NM, Giese, AK, Ikram, MK, Kittner, SJ, McKnight, B, Psaty, BM, Reiner, AP, Sargurupremraj, M, Taylor, KD, Fornage, M, Hamsten, A, Marz, W, Rosendaal, FR, Souto, JC, Dehghan, A, Johnson, AD, Morrison, AC, O'Donnell, CJ, Smith, NL, INVENT Consortium, MEGASTROKE Consortium Intl, Epidemiology, Hematology, Internal Medicine, and Neurology
Subjects: 0301 basic medicine, Male, Candidate gene, Genome-wide association study, Coronary Artery Disease, 030204 cardiovascular system & hematology, Biochemistry, Brain Ischemia, Thrombosis and Hemostasis, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, Cardiac and Cardiovascular Systems, Genetics, education.field_of_study, Kardiologi, Factor VII, Mendelian Randomization Analysis, Hematology, Venous Thromboembolism, Middle Aged, Prognosis, Neoplasm Proteins, DNA-Binding Proteins, Stroke, Phenotype, Female, Co-Repressor Proteins, Immunology, Population, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Mendelian randomization, Gene silencing, Humans, Genetic Predisposition to Disease, cardiovascular diseases, education, Genetic association, Membrane Transport Proteins, Cell Biology, 030104 developmental biology, chemistry, Genetic Loci, Follow-Up Studies, Genome-Wide Association Study
Abstract: Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of nine genome-wide association studies of plasma FVII levels (seven FVII activity and two FVII antigen) among 27,495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the seven studies that measured FVII activity, and a secondary analysis included all nine studies. We provided functional genomic validation for newly identified significant loci by silencing candidate genes in a human liver cell line (HuH7) using siRNA and then measuring F7 mRNA and FVII protein expression. Lastly, we used meta-analysis results to perform Mendelian randomization analysis to estimate the causal effect of FVII activity on coronary artery disease, ischemic stroke, and venous thromboembolism. We identified two novel (REEP3 and JAZF1-AS1) and six known loci associated with FVII activity, explaining 19.0% of the phenotypic variance. Adding FVII antigen data to the meta-analysis did not result in the discovery of further loci. Silencing REEP3 in HuH7 cells upregulated FVII, while silencing JAZF1 downregulated FVII. Mendelian randomization analyses suggest that FVII activity has a positive causal effect on the risk of ischemic stroke. Variants at REEP3 and JAZF1 contribute to FVII activity by regulating F7 expression levels. FVII activity appears to contribute to the etiology of ischemic stroke in the general population.
Published: 2019

16. Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment

Author: Nagtegaal, Paul, Broer, Linda, Zilhao, NR, Jakobsdottir, J, Bishop, CE, Brumat, M, Christiansen, MW, Cocca, M, Gao, Y, Heard-Costa, NL, Evans, DS, Pankratz, N, Pratt, SR, Price, T R, Spankovich, C, Stimson, MR, Valle, K, Vuckovic, D, Wells, H, Eiriksdottir, G, Fransen, E, Ikram, Arfan, Li, CM, Longstreth, WT, Steves, C, van Camp, G, Correa, A, Cruickshanks, KJ, Gasparini, P, Girotto, G, Kaplan, RC, Nalls, M, Schweinfurth, JM, Seshadri, S, Sotoodehnia, N, Tranah, GJ, Uitterlinden, André, Wilson, JG, Gudnason, V, Hoffman, HJ, Williams, FMK, Goedegebure, André, Nagtegaal, Paul, Broer, Linda, Zilhao, NR, Jakobsdottir, J, Bishop, CE, Brumat, M, Christiansen, MW, Cocca, M, Gao, Y, Heard-Costa, NL, Evans, DS, Pankratz, N, Pratt, SR, Price, T R, Spankovich, C, Stimson, MR, Valle, K, Vuckovic, D, Wells, H, Eiriksdottir, G, Fransen, E, Ikram, Arfan, Li, CM, Longstreth, WT, Steves, C, van Camp, G, Correa, A, Cruickshanks, KJ, Gasparini, P, Girotto, G, Kaplan, RC, Nalls, M, Schweinfurth, JM, Seshadri, S, Sotoodehnia, N, Tranah, GJ, Uitterlinden, André, Wilson, JG, Gudnason, V, Hoffman, HJ, Williams, FMK, and Goedegebure, André
Published: 2019

17. Linkage stratification and mutation analysis at the parkin locus identifies mutation positive Parkinsonʼs disease families

Author: Nichols, W C, Pankratz, N, Uniacke, S K, Pauciulo, M W, Halter, C, Rudolph, A, Conneally, P M, and Foroud, T
Published: 2002

18. Overlapping genetic aetiology in adult and paediatric germ cell tumours

Author: Poynter, J.N., primary, Kelley, S., additional, Meredith, J., additional, and Pankratz, N., additional
Published: 2019
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19. Evaluation of mitochondrial DNA copy number estimation techniques

Author: Longchamps, RJ, primary, Castellani, CA, additional, Yang, SY, additional, Newcomb, CE, additional, Sumpter, JA, additional, Lane, J, additional, Grove, ML, additional, Guallar, E, additional, Pankratz, N, additional, Taylor, KD, additional, Rotter, JI, additional, Boerwinkle, E, additional, and Arking, DE, additional
Published: 2019
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20. Insider Ownership, Governance Mechanisms and International Corporate Bond Pricing

Author: Bauer, R., Derwall, J.M.M., Pankratz, N., RS-Research Line Innovation (part of LIRS program), and Department Accounting and Finance
Published: 2017

21. Les mutations germinales du gène CDKN1B sont une cause de maladie de Cushing chez l’enfant

Author: Chasseloup, F., primary, Hernández-Ramírez, L.C., additional, Faucz, F.R., additional, Lodish, M.B., additional, Pankratz, N., additional, Chittiboina, P., additional, Kay, D.M., additional, Giampaolo, T., additional, Bertherat, J., additional, Mills, J.L., additional, and Stratakis, C., additional
Published: 2018
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22. A genome-wide association study for venous thromboembolism: the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium

Author: Tang, W., Teichert, M., Chasman, D.I., Heit, J.A., Morange, P.E., Li, G., Pankratz, N., Leebeek, F.W., Pare, G., Andrade, M. de, Tzourio, C., Psaty, B.M., Basu, S., Ruiter, R. de, Rose, L., Armasu, S.M., Lumley, T., Heckbert, S.R., Uitterlinden, A.G., Lathrop, M., Rice, K.M., Cushman, M., Hofman, A., Lambert, J.C., Glazer, N.L., Pankow, J.S., Witteman, J.C., Amouyel, P., Bis, J.C., Bovill, E.G., Kong, X., Tracy, R.P., Boerwinkle, E., Rotter, J.I., Tregouet, D.A., Loth, D.W., Stricker, B.H., Ridker, P.M., Folsom, A.R., Smith, N.L., Epidemiology, Erasmus School of Social and Behavioural Sciences, Hematology, Cell biology, Cardiology, and Internal Medicine
Subjects: Male, Aging, Implementation Science [NCEBP 3], Venous Thromboembolism, Middle Aged, Polymorphism, Single Nucleotide, Article, Cohort Studies, Meta-Analysis as Topic, Risk Factors, Case-Control Studies, Humans, Regression Analysis, Female, Aged, Genome-Wide Association Study
Abstract: Item does not contain fulltext Venous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two-stage genome-wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community-based studies. Genotypes for genome-wide single-nucleotide polymorphisms (SNPs) were imputed to approximately 2.5 million SNPs in HapMap and association with VTE assessed using study-design appropriate regression methods. Meta-analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (P
Published: 2013

23. Erratum: Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height ((The American Journal of Human Genetics (2010) 88 (6-18))

Author: Lanktree, M, Guo, Y, Murtaza, M, Glessner, J, Bailey, S, Onland-Moret, N, Lettre, G, Ongen, H, Rajagopalan, R, Johnson, T, Shen, H, Nelson, C, Klopp, N, Baumert, J, Padmanabhan, S, Pankratz, N, Pankow, J, Shah, S, Taylor, K, Barnard, J, Peters, B, Maloney, C, Lobmeyer, M, Stanton, A, and Zafarmand, M
Published: 2016

24. Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort

Author: Shen, L., Kim, S., Risacher, S.L., Nho, K., Swaminathan, S., West, J.D., Foroud, T., Pankratz, N., Moore, J.H., Sloan, C.D., Huentelman, M.J., Craig, D.W., DeChairo, B.M., Potkin, S.G., Jack, C.R., Weiner, M.W., Saykin, A.J., Fox, N.C., Neurology, and NCA - Neurodegeneration
Subjects: Male, Candidate gene, Databases, Factual, Genotype, Cognitive Neuroscience, Quantitative Trait Loci, Single-nucleotide polymorphism, Genome-wide association study, Biology, Grey matter, Quantitative trait locus, Bioinformatics, Polymorphism, Single Nucleotide, Article, Apolipoproteins E, Neuroimaging, Alzheimer Disease, medicine, Cluster Analysis, Humans, Genetic Predisposition to Disease, Allele, Aged, Genetic association, Genetics, Magnetic Resonance Imaging, Phenotype, medicine.anatomical_structure, Neurology, Female, Cognition Disorders, Genome-Wide Association Study
Abstract: A genome-wide, whole brain approach to investigate genetic effects on neuroimaging phenotypes for identifying quantitative trait loci is described. The Alzheimer's Disease Neuroimaging Initiative 1.5 T MRI and genetic dataset was investigated using voxel-based morphometry (VBM) and FreeSurfer parcellation followed by genome-wide association studies (GWAS). One hundred forty-two measures of grey matter (GM) density, volume, and cortical thickness were extracted from baseline scans. GWAS, using PLINK, were performed on each phenotype using quality-controlled genotype and scan data including 530,992 of 620,903 single nucleotide polymorphisms (SNPs) and 733 of 818 participants (175 AD, 354 amnestic mild cognitive impairment, MCI, and 204 healthy controls, HC). Hierarchical clustering and heat maps were used to analyze the GWAS results and associations are reported at two significance thresholds (p
Published: 2010

25. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

Author: Huffman, JE, De Vries, PS, Morrison, AC, Sabater-Lleal, M, Kacprowski, T, Auer, PL, Brody, JA, Chasman, DI, Chen, MH, Guo, X, Lin, LA, Marioni, RE, Müller-Nurasyid, M, Yanek, LR, Pankratz, N, Grove, ML, De Maat, MPM, Cushman, M, Wiggins, KL, Qi, L, Sennblad, B, Harris, SE, Polasek, O, Riess, H, Rivadeneira, F, Rose, LM, Goel, A, Taylor, KD, Teumer, A, Uitterlinden, AG, Vaidya, D, Yao, J, Tang, W, Levy, D, Waldenberger, M, Becker, DM, Folsom, AR, Giulianini, F, Greinacher, A, Hofman, A, Huang, CC, Kooperberg, C, Silveira, A, Starr, JM, Strauch, K, Strawbridge, RJ, Wright, AF, McKnight, B, Franco, OH, Zakai, N, Mathias, RA, Psaty, BM, Ridker, PM, Tofler, GH, Völker, U, Watkins, H, Fornage, M, Hamsten, A, Deary, IJ, Boerwinkle, E, Koenig, W, Rotter, JI, Hayward, C, Dehghan, A, Reiner, AP, and O'Donnell, CJ
Abstract: © 2015, American Society of Hematology. All rights reserved. Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and
Published: 2015

26. GCT-06 - Overlapping genetic aetiology in adult and paediatric germ cell tumours

Author: Poynter, J.N., Kelley, S., Meredith, J., and Pankratz, N.
Published: 2019
Full Text: View/download PDF

27. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease

Author: Nalls, M.A. Pankratz, N. Lill, C.M. Do, C.B. Hernandez, D.G. Saad, M. Destefano, A.L. Kara, E. Bras, J. Sharma, M. Schulte, C. Keller, M.F. Arepalli, S. Letson, C. Edsall, C. Stefansson, H. Liu, X. Pliner, H. Lee, J.H. Cheng, R. Ikram, M.A. Ioannidis, J.P.A. Hadjigeorgiou, G.M. Bis, J.C. Martinez, M. Perlmutter, J.S. Goate, A. Marder, K. Fiske, B. Sutherland, M. Xiromerisiou, G. Myers, R.H. Clark, L.N. Stefansson, K. Hardy, J.A. Heutink, P. Chen, H. Wood, N.W. Houlden, H. Payami, H. Brice, A. Scott, W.K. Gasser, T. Bertram, L. Eriksson, N. Foroud, T. Singleton, A.B. Plagnol, V. Sheerin, U.-M. Simón-Sánchez, J. Lesage, S. Sveinbjörnsdóttir, S. Barker, R. Ben-Shlomo, Y. Berendse, H.W. Berg, D. Bhatia, K. de Bie, R.M.A. Biffi, A. Bloem, B. Bochdanovits, Z. Bonin, M. Bras, J.M. Brockmann, K. Brooks, J. Burn, D.J. Charlesworth, G. Chinnery, P.F. Chong, S. Clarke, C.E. Cookson, M.R. Cooper, J.M. Corvol, J.C. Counsell, C. Damier, P. Dartigues, J.-F. Deloukas, P. Deuschl, G. Dexter, D.T. van Dijk, K.D. Dillman, A. Durif, F. Dürr, A. Edkins, S. Evans, J.R. Foltynie, T. Dong, J. Gardner, M. Gibbs, J.R. Gray, E. Guerreiro, R. Harris, C. van Hilten, J.J. Hofman, A. Hollenbeck, A. Holton, J. Hu, M. Huang, X. Wurster, I. Mätzler, W. Hudson, G. Hunt, S.E. Huttenlocher, J. Illig, T. Jónsson, P.V. Lambert, J.-C. Langford, C. Lees, A. Lichtner, P. Limousin, P. Lopez, G. Lorenz, D. McNeill, A. Moorby, C. Moore, M. Morris, H.R. Morrison, K.E. Mudanohwo, E. O’sullivan, S.S. Pearson, J. Pétursson, H. Pollak, P. Post, B. Potter, S. Ravina, B. Revesz, T. Riess, O. Rivadeneira, F. Rizzu, P. Ryten, M. Sawcer, S. Schapira, A. Scheffer, H. Shaw, K. Shoulson, I. Sidransky, E. Smith, C. Spencer, C.C.A. Stefánsson, H. Bettella, F. Stockton, J.D. Strange, A. Talbot, K. Tanner, C.M. Tashakkori-Ghanbaria, A. Tison, F. Trabzuni, D. Traynor, B.J. Uitterlinden, A.G. Velseboer, D. Vidailhet, M. Walker, R. van de Warrenburg, B. Wickremaratchi, M. Williams, N. Williams-Gray, C.H. Winder-Rhodes, S. Stefánsson, K. Hardy, J. Factor, S. Higgins, D. Evans, S. Shill, H. Stacy, M. Danielson, J. Marlor, L. Williamson, K. Jankovic, J. Hunter, C. Simon, D. Ryan, P. Scollins, L. Saunders-Pullman, R. Boyar, K. Costan-Toth, C. Ohmann, E. Sudarsky, L. Joubert, C. Friedman, J. Chou, K. Fernandez, H. Lannon, M. Galvez-Jimenez, N. Podichetty, A. Thompson, K. Lewitt, P. Deangelis, M. O'brien, C. Seeberger, L. Dingmann, C. Judd, D. Marder, K. Fraser, J. Harris, J. Bertoni, J. Peterson, C. Rezak, M. Medalle, G. Chouinard, S. Panisset, M. Hall, J. Poiffaut, H. Calabrese, V. Roberge, P. Wojcieszek, J. Belden, J. Jennings, D. Marek, K. Mendick, S. Reich, S. Dunlop, B. Jog, M. Horn, C. Uitti, R. Turk, M. Ajax, T. Mannetter, J. Sethi, K. Carpenter, J. Dill, B. Hatch, L. Ligon, K. Narayan, S. Blindauer, K. Abou-Samra, K. Petit, J. Elmer, L. Aiken, E. Davis, K. Schell, C. Wilson, S. Velickovic, M. Koller, W. Phipps, S. Feigin, A. Gordon, M. Hamann, J. Licari, E. Marotta-Kollarus, M. Shannon, B. Winnick, R. Simuni, T. Videnovic, A. Kaczmarek, A. Williams, K. Wolff, M. Rao, J. Cook, M. Fernandez, M. Kostyk, S. Hubble, J. Campbell, A. Reider, C. Seward, A. Camicioli, R. Carter, J. Nutt, J. Andrews, P. Morehouse, S. Stone, C. Mendis, T. Grimes, D. Alcorn-Costa, C. Gray, P. Haas, K. Vendette, J. Sutton, J. Hutchinson, B. Young, J. Rajput, A. Klassen, L. Shirley, T. Manyam, B. Simpson, P. Whetteckey, J. Wulbrecht, B. Truong, D. Pathak, M. Frei, K. Luong, N. Tra, T. Tran, A. Vo, J. Lang, A. Kleiner-Fisman, G. Nieves, A. Johnston, L. So, J. Podskalny, G. Giffin, L. Atchison, P. Allen, C. Martin, W. Wieler, M. Suchowersky, O. Furtado, S. Klimek, M. Hermanowicz, N. Niswonger, S. Shults, C. Fontaine, D. Aminoff, M. Christine, C. Diminno, M. Hevezi, J. Dalvi, A. Kang, U. Richman, J. Uy, S. Sahay, A. Gartner, M. Schwieterman, D. Hall, D. Leehey, M. Culver, S. Derian, T. Demarcaida, T. Thurlow, S. Rodnitzky, R. Dobson, J. Lyons, K. Pahwa, R. Gales, T. Thomas, S. Shulman, L. Weiner, W. Dustin, K. Singer, C. Zelaya, L. Tuite, P. Hagen, V. Rolandelli, S. Schacherer, R. Kosowicz, J. Gordon, P. Werner, J. Serrano, C. Roque, S. Kurlan, R. Berry, D. Gardiner, I. Hauser, R. Sanchez-Ramos, J. Zesiewicz, T. Delgado, H. Price, K. Rodriguez, P. Wolfrath, S. Pfeiffer, R. Davis, L. Pfeiffer, B. Dewey, R. Hayward, B. Johnson, A. Meacham, M. Estes, B. Walker, F. Hunt, V. O'neill, C. Racette, B. Swisher, L. Dijamco, C. Conley, E.D. Dorfman, E. Tung, J.Y. Hinds, D.A. Mountain, J.L. Wojcicki, A. Lew, M. Klein, C. Golbe, L. Growdon, J. Wooten, G.F. Watts, R. Guttman, M. Goldwurm, S. Saint-Hilaire, M.H. Baker, K. Litvan, I. Nicholson, G. Nance, M. Drasby, E. Isaacson, S. Burn, D. Pramstaller, P. Al-Hinti, J. Moller, A. Sherman, S. Roxburgh, R. Slevin, J. Perlmutter, J. Mark, M.H. Huggins, N. Pezzoli, G. Massood, T. Itin, I. Corbett, A. Chinnery, P. Ostergaard, K. Snow, B. Cambi, F. Kay, D. Samii, A. Agarwal, P. Roberts, J.W. Higgins, D.S. Molho, E. Rosen, A. Montimurro, J. Martinez, E. Griffith, A. Kusel, V. Yearout, D. Factor, S. Zabetian, C. Clark, L.N. Liu, X. Lee, J.H. Cheng Taub, R. Louis, E.D. Cote, L.J. Waters, C. Ford, B. Fahn, S. Vance, J.M. Beecham, G.W. Martin, E.R. Nuytemans, K. Pericak-Vance, M.A. Haines, J.L. Destefano, A. Seshadri, S. Choi, S.H. Frank, S. Bis, J.C. Psaty, B.M. Rice, K. Longstreth, W.T., Jr. Ton, T.G.N. Jain, S. van Duijn, C.M. Uitterlinden, A.G. Verlinden, V.J. Koudstaal, P.J. Singleton, A. Cookson, M. Gibbs, J.R. Hernandez, D. Nalls, M. Zonderman, A. Ferrucci, L. Johnson, R. Longo, D. O'brien, R. Traynor, B. Troncoso, J. van der Brug, M. Zielke, R. Weale, M. Ramasamy, A. Dardiotis, E. Tsimourtou, V. Spanaki, C. Plaitakis, A. Bozi, M. Stefanis, L. Vassilatis, D. Koutsis, G. Panas, M. Hadjigeorgiou, G.M. Lunnon, K. Lupton, M. Powell, J. Parkkinen, L. Ansorge, O. International Parkinson's Disease Genomics Consortium (IPDGC) Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI) 23andMe GenePD NeuroGenetics Research Consortium (NGRC) Hussman Institute of Human Genomics (HIHG) The Ashkenazi Jewish Dataset Investigator Cohorts for Health Aging Research in Genetic Epidemiology (CHARGE) North American Brain Expression Consortium (NABEC) United Kingdom Brain Expression Consortium (UKBEC) Greek Parkinson's Disease Consortium Alzheimer Genetic Analysis Group
Abstract: We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10-16). We also show six risk loci associated with proximal gene expression or DNA methylation. © 2014 Nature America, Inc. All rights reserved.
Published: 2014

28. NeuroX, a fast and efficient genotyping platform for investigation of neurodegenerative diseases

Author: Nalls, M.A., Bras, J., Hernandez, D.G., Keller, M.F., Majounie, E., Renton, A.E., Saad, M., Jansen, I., Guerreiro, R., Lubbe, S., Plagnol, V., Gibbs, J.R., Schulte, C., Pankratz, N., Sutherland, M., Bertram, L., Lill, C.M., DeStefano, A.L., Faroud, T., Eriksson, N., Tung, J.Y., Edsall, C., Nichols, N., Brooks, J., Arepalli, S., Pliner, H., Letson, C., Heutink, P., Martinez, M., Gasser, T., Traynor, B.J., Wood, N., Hardy, J., Singleton, A.B., Bloem, B.R., Post, B., Scheffer, H., Warrenburg, B.P.C. van de, et al., Nalls, M.A., Bras, J., Hernandez, D.G., Keller, M.F., Majounie, E., Renton, A.E., Saad, M., Jansen, I., Guerreiro, R., Lubbe, S., Plagnol, V., Gibbs, J.R., Schulte, C., Pankratz, N., Sutherland, M., Bertram, L., Lill, C.M., DeStefano, A.L., Faroud, T., Eriksson, N., Tung, J.Y., Edsall, C., Nichols, N., Brooks, J., Arepalli, S., Pliner, H., Letson, C., Heutink, P., Martinez, M., Gasser, T., Traynor, B.J., Wood, N., Hardy, J., Singleton, A.B., Bloem, B.R., Post, B., Scheffer, H., Warrenburg, B.P.C. van de, and et al.
Abstract: Contains fulltext : 153490.pdf (publisher's version ) (Closed access), Our objective was to design a genotyping platform that would allow rapid genetic characterization of samples in the context of genetic mutations and risk factors associated with common neurodegenerative diseases. The platform needed to be relatively affordable, rapid to deploy, and use a common and accessible technology. Central to this project, we wanted to make the content of the platform open to any investigator without restriction. In designing this array we prioritized a number of types of genetic variability for inclusion, such as known risk alleles, disease-causing mutations, putative risk alleles, and other functionally important variants. The array was primarily designed to allow rapid screening of samples for disease-causing mutations and large population studies of risk factors. Notably, an explicit aim was to make this array widely available to facilitate data sharing across and within diseases. The resulting array, NeuroX, is a remarkably cost and time effective solution for high-quality genotyping. NeuroX comprises a backbone of standard Illumina exome content of approximately 240,000 variants, and over 24,000 custom content variants focusing on neurologic diseases. Data are generated at approximately $50-$60 per sample using a 12-sample format chip and regular Infinium infrastructure; thus, genotyping is rapid and accessible to many investigators. Here, we describe the design of NeuroX, discuss the utility of NeuroX in the analyses of rare and common risk variants, and present quality control metrics and a brief primer for the analysis of NeuroX derived data.
Published: 2015

29. Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals

Author: Guo, Y., Lanktree, M. B., Taylor, K. C., Hakonarson, H., Lange, L. A., Keating, B. J., Fairfax, B. P., Elbers, C. C., Barnard, J., Farrall, M., Padmanabhan, S., Baumert, J., Castillo, B. A., Gaunt, T. R., Gong, Y., Rajagopalan, R., Romaine, S. P., Kumari, M., Rafelt, S., Smith, E. N., Li, Y. R., Sivapalaratnam, S., van Iperen, E. P., Speliotes, E. K., Toskala, E., Zhang, L., Ochs-Balcom, H. M., Bhangale, T. R., Chandrupatla, H. R., Drenos, F., Gieger, C., Gupta, J., Johnson, T., Kleber, M. E., Makino, S., Mangino, M., Meng, Y., Nelson, C. P., Pankow, J. S., Pankratz, N., Price, T. S., Shaffer, J., Shen, H., Tischfield, S., Tomaszewski, M., Atwood, L. D., Bailey, K. M., Balasubramanyam, A., Baldwin, C. T., Basart, H., Bauer, F., Behr, E. R., Beitelshees, A. L., Berenson, G. S., Beresford, S. A., Bezzina, C. R., Bhatt, D. L., Boer, J. M., Braund, P. S., Burke, G. L., Burkley, B., Carty, C., Chen, W., Clarke, R., Cooper-DeHoff, R. M., Curtis, S. P., de Bakker, P. I., de Jong, J. S., Delles, C., Dominiczak, A. F., Duggan, D., Feldman, H. I., Furlong, C. E., Gorski, M. M., Gums, J. G., Hardwick, R., Hastie, C., Heid, I. M., Huang, G.-H., Huggins, G. S., Humphries, S. E., Kirkland, S. A., Kivimaki, M., Klein, R., Klein, B. E., Knowler, W. C., Kottke-Marchant, K., LaCroix, A. Z., Langaee, T. Y., Li, M., Lyon, H. N., Maiwald, S., Marshall, J. K., Mehta, A., Meijs, M. F., Melander, O., Meyer, N., Mitra, N., Molony, C. M., Morrow, D. A., Murugesan, G., Newhouse, S. J., Nieto, J. F., Onland-Moret, N. C., Ouwehand, W. H., Palmen, J., Pepine, C. J., Ranchalis, J., Rosas, S. E., Rosenthal, E. A., Scharnagl, H., Schork, N. J., Schreiner, P. J., Shah, T., Shashaty, M., Shimbo, D., Srinivasan, S. R., Thomas, F., Tobin, M. D., Tsai, M. Y., Verschuren, W. M. M., Wagenknecht, L. E., Winkelmann, B. R., Young, T., Yusuf, S., Zafarmand, M. H., Zmuda, J. M., Zwinderman, A. H., Anand, S. S., Balmforth, A. J., Boehm, B. O., Boerwinkle, E., Burton, P. R., Cappola, T. P., Casas, J. P., Caulfield, M. J., Christiani, D. C., Christie, J., Cruickshanks, K. J., Davey-Smith, G., Davidson, K. W., Day, I. N., Doevendans, P. A., Dorn, G. W., FitzGerald, G. A., Hall, A. S., Hingorani, A. D., Hirschhorn, J. N., Hofker, M. H., Hovingh, K. G., Illig, T., Jamshidi, Y., Jarvik, G. P., Johnson, J. A., Kanetsky, P. A., Kastelein, J. J., Koenig, W., Lawlor, D. A., Marz, W., McCaffery, J., Mega, J. L., Mitchell, B. D., Murray, S. S., O'Connell, J. R., Patel, S. R., Peters, A., Pettinger, M., Rader, D. J., Redline, S., Reilly, M. P., Sabatine, M. S., Schadt, E. E., Shuldiner, A. R., Silverstein, R. L., Spector, T. D., Taylor, H. A., Thorand, B., Trip, M. D., Watkins, H., Wichmann, H.- E., Fox, C. S., Grant, S. F., Peter, I., Talmud, P. J., Munroe, P. B., Wilson, J. G., Knight, J. C., Samani, N. J., Hegele, R. A., Asselbergs, F. W., Monda, K. L., van der Schouw, Y. T., Demerath, E. W., Wijmenga, C., Timpson, N. J., Reiner, A. P., North, K. E., Papanicolaou, G. J., Lange , L. A., Keating , B. J., Vascular Medicine, Amsterdam Public Health, Epidemiology and Data Science, Graduate School, Other departments, Amsterdam Cardiovascular Sciences, Cardiology, Other Research, and Public and occupational health
Subjects: Population, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, SH2B1, Genotype, Ethnicity, Genetics, Humans, education, Molecular Biology, Gene, Genetics (clinical), 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, Association Studies Articles, General Medicine, Melanocortin 4 receptor, 030217 neurology & neurosurgery
Abstract: Recent genetic association studies have made progress in uncovering components of the genetic architecture of the body mass index (BMI). We used the ITMAT-Broad-Candidate Gene Association Resource (CARe) (IBC) array comprising up to 49 320 single nucleotide polymorphisms (SNPs) across ~2100 metabolic and cardiovascular-related loci to genotype up to 108 912 individuals of European ancestry (EA), African-Americans, Hispanics and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P < 2.40E-06), we identify novel BMI associations in loci translocase of outer mitochondrial membrane 40 homolog (yeast) - apolipoprotein E - apolipoprotein C-I (TOMM40-APOE-APOC1) (rs2075650, P = 2.95E-10), sterol regulatory element binding transcription factor 2 (SREBF2, rs5996074, P = 9.43E-07) and neurotrophic tyrosine kinase, receptor, type 2 [NTRK2, a brain-derived neurotrophic factor (BDNF) receptor gene, rs1211166, P = 1.04E-06] in the Phase IV meta-analysis. Of 10 loci with previous evidence for BMI association represented on the IBC array, eight were replicated, with the remaining two showing nominal significance. Conditional analyses revealed two independent BMI-associated signals in BDNF and melanocortin 4 receptor (MC4R) regions. Of the 11 array-wide significant SNPs, three are associated with gene expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B adaptor protein 1 (SH2B1) notably being associated with the expression of multiple genes in cis. These multi-ethnic meta-analyses expand our knowledge of BMI genetics.
Published: 2013

30. Erratum: Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height ((The American Journal of Human Genetics (2010) 88 (6-18))

Author: Lanktree, MB, Guo, Y, Murtaza, M, Glessner, JT, Bailey, SD, Onland-Moret, NC, Lettre, G, Ongen, H, Rajagopalan, R, Johnson, T, Shen, H, Nelson, CP, Klopp, N, Baumert, J, Padmanabhan, S, Pankratz, N, Pankow, JS, Shah, S, Taylor, K, Barnard, J, Peters, BJ, Maloney, CM, Lobmeyer, MT, Stanton, A, Zafarmand, MH, Romaine, SPR, Mehta, A, Van Iperen, EPA, Gong, Y, Price, TS, Smith, EN, Kim, CE, Li, YR, Asselbergs, FW, Atwood, LD, Bailey, KM, Bhatt, D, Bauer, F, Behr, ER, Bhangale, T, Boer, JMA, Boehm, BO, Bradfield, JP, Brown, M, Braund, PS, Burton, PR, Carty, C, Chandrupatla, HR, Chen, W, Connell, J, Dalgeorgou, C, De Boer, A, Drenos, F, Elbers, CC, Fang, JC, Fox, CS, Frackelton, EC, Fuchs, B, Furlong, CE, Gibson, Q, Gieger, C, Goel, A, Grobbee, DE, Hastie, C, Howard, PJ, Huang, G-H, Johnson, WC, Li, Q, Kleber, ME, Klein, BEK, Klein, R, Kooperberg, C, Ky, B, Lacroix, A, Lanken, P, Lathrop, M, Li, M, Marshall, V, Melander, O, Mentch, FD, Meyer, NJ, Monda, KL, Montpetit, A, Murugesan, G, Nakayama, K, Nondahl, D, Onipinla, A, Rafelt, S, Newhouse, SJ, Otieno, FG, Patel, SR, Putt, ME, Rodriguez, S, Safa, RN, Sawyer, DB, Schreiner, PJ, Simpson, C, Sivapalaratnam, S, Srinivasan, SR, Suver, C, Swergold, G, Sweitzer, NK, Thomas, KA, Thorand, B, Timpson, NJ, Tischfield, S, Tobin, M, Tomaszewski, M, Verschuren, WMM, Wallace, C, Winkelmann, B, Zhang, H, Zheng, D, Zhang, L, Zmuda, JM, Clarke, R, Balmforth, AJ, Danesh, J, Day, IN, Schork, NJ, De Bakker, PIW, Delles, C, Duggan, D, Hingorani, AD, Hirschhorn, JN, Hofker, MH, Humphries, SE, Kivimaki, M, Lawlor, DA, Kottke-Marchant, K, Mega, JL, Mitchell, BD, Morrow, DA, Palmen, J, Redline, S, Shields, DC, Shuldiner, AR, Sleiman, PM, Smith, GD, Farrall, M, Jamshidi, Y, Christiani, DC, Casas, JP, Hall, AS, Doevendans, PA, Christie, JD, Berenson, GS, Murray, SS, Illig, T, Dorn, GW, Cappola, TP, Boerwinkle, E, Sever, P, Rader, DJ, Reilly, MP, Caulfield, M, Talmud, PJ, Topol, E, Engert, JC, Wang, K, Dominiczak, A, Hamsten, A, Curtis, SP, Silverstein, RL, Lange, LA, Sabatine, MS, Trip, M, Saleheen, D, Peden, JF, Cruickshanks, KJ, März, W, O'Connell, JR, Klungel, OH, Wijmenga, C, Maitland-Van Der Zee, AH, Schadt, EE, Johnson, JA, Jarvik, GP, Papanicolaou, GJ, Grant, SFA, Munroe, PB, North, KE, Samani, NJ, Koenig, W, Gaunt, TR, Anand, SS, Van Der Schouw, YT, Soranzo, N, Fitzgerald, GA, Reiner, A, Hegele, RA, Hakonarson, H, and Keating, BJ
Published: 2012

31. Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database

Author: Lill, C., Roehr, C., McQueen, M., Kavvoura, F., Bagade, S., Schjeide, B., Schjeide, L., Meissner, E., Zauft, U., Allen, N., Liu, T., Schilling, M., Anderson, K., Beecham, G., Berg, D., Biernacka, J., Brice, A., DeStefano, A., Do, C., Eriksson, N., Factor, S., Farrer, M., Foroud, T., Gasser, T., Hamza, T., Hardy, J., Heutink, P., Hill-Burns, E., Klein, C., Latourelle, J., Maraganore, D., Martin, E., Martinez, M., Myers, R., Nalls, M., Pankratz, N., Payami, H., Satake, W., Scott, W., Sharma, M., Singleton, A., Stefansson, K., Toda, T., Tung, J., Vance, J., Wood, N., Zabetian, C., Young, P., Tanzi, R., Khoury, M., Zipp, F., Lehrach, H., Ioannidis, J., Bertram, L., Parkinson's, G., IPDGC, Consortium, P., WTCCC2, 23andMe, The Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium, The International Parkinson's Disease Genomics Consortium (IPDGC), The Parkinson's Disease GWAS Consortium, The Wellcome Trust Case Control Consortium 2 (WTCCC2), Human genetics, and NCA - Neurodegeneration
Subjects: Internet, Epidemiology, Genome, Human, Parkinson Disease, QH426-470, Polymorphism, Single Nucleotide, Neurology, genetics [Parkinson Disease], Databases, Genetic, Genetics, Medicine, Humans, ddc:610, Research Article, Genome-Wide Association Study
Abstract: More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of ∼27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P, Author Summary The genetic basis of Parkinson's disease is complex, i.e. it is determined by a number of different disease-causing and disease-predisposing genes. Especially the latter have proven difficult to find, evidenced by more than 800 published genetic association studies, typically showing discrepant results. To facilitate the interpretation of this large and continuously increasing body of data, we have created a freely available online database (“PDGene”: http://www.pdgene.org) which provides an exhaustive account of all published genetic association studies in PD. One particularly useful feature is the calculation and display of up-to-date summary statistics of published data for overlapping DNA sequence variants (polymorphisms). These meta-analyses revealed eleven gene loci that showed a statistically very significant (P
Published: 2012

32. A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly

Author: Ho, A. J., Stein, J. L., Hua, X., Lee, S., Hibar, D. P., Leow, A. D., Dinov, I. D., Toga, A. W., Saykin, A. J., Shen, L., Foroud, T., Pankratz, N., Huentelman, M. J., Craig, D. W., Gerber, J. D., Allen, A. N., Corneveaux, J. J., Stephan, D. A., DeCarli, C. S., DeChairo, B. M., Potkin, S. G., Jack, C. R., Weiner, M. W., Raji, C. A., Lopez, O. L., Becker, J. T., Carmichael, O. T., Thompson, P. M., the Alzheimer's Disease Neuroimaging Initiative, Weiner, M., Thal, L., Petersen, R., Jagust, W., Trojanowki, J., Beckett, L., Green, R. C., Gamst, A., Potter, W. Z., Montine, T., Anders, D., Bernstein, M., Felmlee, J., Fox, N., Thompson, P., Schuff, N., Alexander, G., Bandy, D., Koeppe, R. A., Foster, N., Reiman, E. M., Chen, K., Shaw, L., Lee, V. M.- Y., Korecka, M., Crawford, K., Neu, S., Harvey, D., Kornak, J., Kachaturian, Z., Frank, R., Snyder, P. J., Molchan, S., Kaye, J., Vorobik, R., Quinn, J., Schneider, L., Pawluczyk, S., Spann, B., Fleisher, A. S., Vanderswag, H., Heidebrink, J. L., Lord, J. L., Johnson, K., Doody, R. S., Villanueva-Meyer, J., Chowdhury, M., Stern, Yaakov, Honig, L. S., Bell, K. L., Morris, J. C., Mintun, M. A., Schneider, S., Marson, D., Griffith, R., Badger, B., Grossman, H., Tang, C., Stern, J., deToledo-Morrell, L., Shah, R. C., Bach, J., Duara, R., Isaacson, R., Strauman, S., Albert, M. S., Pedroso, J., Toroney, J., Rusinek, H., de Leon, M. J., De Santi, S. M., Doraiswamy, P. M., Petrella, J. R., Aiello, M., Clark, C. M., Pham, C., Nunez, J., Smith, C. D., Given II, C. A., Hardy, P., DeKosky, S. T., Oakley, M., Simpson, D. M., Ismail, M. S., Porsteinsson, A., McCallum, C., Cramer, S. C., Mulnard, R. A., McAdams-Ortiz, C., Diaz-Arrastia, R., Martin-Cook, K., DeVous, M., Levey, A. I., Lah, J. J., Cellar, J. S., Burns, J. M., Anderson, H. S., Laubinger, M. M., Bartzokis, G., Silverman, D. H. S., Lu, P. H., Fletcher, R., Parfitt, F., Johnson, H., Farlow, M., Herring, S., Hake, A. M., van Dyck, C. H., MacAvoy, M. G., Bifano, L. A., Chertkow, H., Bergman, H., Hosein, C., Black, S., Graham, S., Caldwell, C., Feldman, H., Assaly, M., Hsiung, G.-Y. R., Kertesz, A., Rogers, J., Trost, D., Bernick, C., Gitelman, D., Johnson, N., Mesulam, M., Sadowsky, C., Villena, T., Mesner, S., Aisen, P. S., Johnson, K. B., Behan, K. E., Sperling, R. A., Rentz, D. M., Johnson, K. A., Rosen, A., Tinklenberg, J., Ashford, W., Sabbagh, M., Connor, D., Obradov, S., Killiany, R., Norbash, A., Obisesan, T. O., Jayam-Trouth, A., Wang, P., Auchus, A. P., Huang, J., Friedland, R. P., DeCarli, C., Fletcher, E., Carmichael, O., Kittur, S., Mirje, S., Johnson, S. C., Borrie, M., Lee, T.-Y., Asthana, S., Carlsson, C. M., Highum, D., Preda, A., Nguyen, D., Tariot, P. N., Hendin, B. A., Scharre, D. W., Kataki, M., Beversdorf, D. Q., Zimmerman, E. A., Celmins, D., Brown, A. D., Gandy, S., Marenberg, M. E., Rovner, B. W., Pearlson, G., Blank, K., Anderson, K., Santulli, R. B., Pare, N., Williamson, J. D., Sink, K. M., Potter, H., Ashok Raj, B., Giordano, A., Ott, B. R., Wu, C.-K., Cohen, R., and Wilks, K. L.
Published: 2010
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33. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

Author: Nalls, M.A., Pankratz, N., Lill, C.M., Do, C.B., Hernandez, D.G., Saad, M., DeStefano, A.L., Kara, E., Bras, J., Sharma, M., Schulte, C., Keller, M.F., Arepalli, S., Letson, C., Edsall, C., Stefansson, H., Liu, X., Pliner, H., Lee, J.H. van der, Cheng, R., Ikram, M.A., Ioannidis, J.P., Hadjigeorgiou, G.M., Bis, J.C., Martinez, M., Perlmutter, J.S., Goate, A., Marder, K., Fiske, B., Sutherland, M., Xiromerisiou, G., Myers, R.H., Clark, L.N., Stefansson, K., Hardy, J.A., Heutink, P., Chen, H., Wood, N.W., Houlden, H., Payami, H., Brice, A., Scott, W.K., Gasser, T., Bertram, L., Eriksson, N., Foroud, T., Singleton, A.B., Scheffer, H., Warrenburg, B.P.C. van de, et al., Nalls, M.A., Pankratz, N., Lill, C.M., Do, C.B., Hernandez, D.G., Saad, M., DeStefano, A.L., Kara, E., Bras, J., Sharma, M., Schulte, C., Keller, M.F., Arepalli, S., Letson, C., Edsall, C., Stefansson, H., Liu, X., Pliner, H., Lee, J.H. van der, Cheng, R., Ikram, M.A., Ioannidis, J.P., Hadjigeorgiou, G.M., Bis, J.C., Martinez, M., Perlmutter, J.S., Goate, A., Marder, K., Fiske, B., Sutherland, M., Xiromerisiou, G., Myers, R.H., Clark, L.N., Stefansson, K., Hardy, J.A., Heutink, P., Chen, H., Wood, N.W., Houlden, H., Payami, H., Brice, A., Scott, W.K., Gasser, T., Bertram, L., Eriksson, N., Foroud, T., Singleton, A.B., Scheffer, H., Warrenburg, B.P.C. van de, and et al.
Abstract: 1 september 2014, Item does not contain fulltext, We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 x 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.
Published: 2014

34. Translation initiator EIF4G1 mutations in familial Parkinson disease

Author: Chartier Harlin, M, Dachsel, Jc, Vilariño Güell, C, Lincoln, Sj, Leprêtre, F, Hulihan, Mm, Kachergus, J, Milnerwood, Aj, Tapia, L, Song, M, Le Rhun, E, Mutez, E, Larvor, L, Duflot, A, Vanbesien Mailliot, C, Kreisler, A, Ross, Oa, Nishioka, K, Soto Ortolaza, Ai, Cobb, Sa, Melrose, Hl, Behrouz, B, Keeling, Bh, Bacon, Ja, Hentati, E, Williams, L, Yanagiya, A, Sonenberg, N, Lockhart, Pj, Zubair, Ac, Uitti, Rj, Aasly, Jo, Krygowska Wajs, A, Opala, G, Wszolek, Zk, Frigerio, R, Maraganore, Dm, Gosal, D, Lynch, T, Hutchinson, M, Bentivoglio, Anna Rita, Valente, Enza Maria, Nichols, Wc, Pankratz, N, Foroud, T, Gibson, Ra, Hentati, F, Dickson, Dw, Destée, A, Farrer, Mj, Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X), Chartier Harlin, M, Dachsel, Jc, Vilariño Güell, C, Lincoln, Sj, Leprêtre, F, Hulihan, Mm, Kachergus, J, Milnerwood, Aj, Tapia, L, Song, M, Le Rhun, E, Mutez, E, Larvor, L, Duflot, A, Vanbesien Mailliot, C, Kreisler, A, Ross, Oa, Nishioka, K, Soto Ortolaza, Ai, Cobb, Sa, Melrose, Hl, Behrouz, B, Keeling, Bh, Bacon, Ja, Hentati, E, Williams, L, Yanagiya, A, Sonenberg, N, Lockhart, Pj, Zubair, Ac, Uitti, Rj, Aasly, Jo, Krygowska Wajs, A, Opala, G, Wszolek, Zk, Frigerio, R, Maraganore, Dm, Gosal, D, Lynch, T, Hutchinson, M, Bentivoglio, Anna Rita, Valente, Enza Maria, Nichols, Wc, Pankratz, N, Foroud, T, Gibson, Ra, Hentati, F, Dickson, Dw, Destée, A, Farrer, Mj, and Bentivoglio, Anna Rita (ORCID:0000-0002-9663-095X)
Abstract: Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.
Published: 2011

35. Parkin dosage mutations have greater pathogenicity in familial PD than simple sequence mutations.

Author: Pankratz N, Kissell DK, Pauciulo MW, Halter CA, Rudolph A, Pfeiffer RF, Marder KS, Foroud T, Nichols WC, Parkinson Study Group-PROGENI Investigators, Pankratz, N, Kissell, D K, Pauciulo, M W, Halter, C A, Rudolph, A, Pfeiffer, R F, Marder, K S, Foroud, T, and Nichols, W C
Published: 2009
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36. Factors Related to Fungiform Papillae Density: The Beaver Dam Offspring Study

Author: Fischer, M. E., primary, Cruickshanks, K. J., additional, Schubert, C. R., additional, Pinto, A., additional, Klein, R., additional, Pankratz, N., additional, Pankow, J. S., additional, and Huang, G.-H., additional
Published: 2013
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37. Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease.

Author: Foroud T, Uniacke SK, Liu L, Pankratz N, Rudolph A, Halter C, Shults C, Marder K, Conneally PM, Nichols WC, Parkinson Study Group, Foroud, T, Uniacke, S K, Liu, L, Pankratz, N, Rudolph, A, Halter, C, Shults, C, Marder, K, and Conneally, P M
Published: 2003
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38. MUTATIONS IN GBA ARE ASSOCIATED WITH FAMILIAL PARKINSON DISEASE SUSCEPTIBILITY AND AGE AT ONSET

Author: Sidransky, E., primary, Samaddar, T., additional, Tayebi, N., additional, Nichols, W. C., additional, Pankratz, N., additional, and Foroud, T., additional
Published: 2009
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39. Variation in GIGYF2 is not associated with Parkinson disease

Author: Nichols, W. C., primary, Kissell, D. K., additional, Pankratz, N., additional, Pauciulo, M. W., additional, Elsaesser, V. E., additional, Clark, K. A., additional, Halter, C. A., additional, Rudolph, A., additional, Wojcieszek, J., additional, Pfeiffer, R. F., additional, and Foroud, T., additional
Published: 2009
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40. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset

Author: Nichols, W. C., primary, Pankratz, N., additional, Marek, D. K., additional, Pauciulo, M. W., additional, Elsaesser, V. E., additional, Halter, C. A., additional, Rudolph, A., additional, Wojcieszek, J., additional, Pfeiffer, R. F., additional, and Foroud, T., additional
Published: 2009
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41. LRRK2 MUTATION ANALYSIS IN PARKINSON DISEASE FAMILIES WITH EVIDENCE OF LINKAGE TO PARK8

Author: Bonifati, V., primary, Wu-Chou, Y-H, additional, Schweiger, D., additional, Fonzo, A. D., additional, Lu, C-S, additional, Oostra, B., additional, Nichols, W .C., additional, Elsaesser, V .E., additional, Pankratz, N ., additional, Pauciulo, M .W., additional, Marek, D .K., additional, Halter, C .A., additional, Rudolph, A ., additional, and Foroud, T ., additional
Published: 2008
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42. LRRK2 mutation analysis in Parkinson disease families with evidence of linkage to PARK8

Author: Nichols, W. C., primary, Elsaesser, V. E., additional, Pankratz, N., additional, Pauciulo, M. W., additional, Marek, D. K., additional, Halter, C. A., additional, Rudolph, A., additional, Shults, C. W., additional, and Foroud, T., additional
Published: 2007
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43. A mutation in myotilin causes spheroid body myopathy

Author: Foroud, T., primary, Pankratz, N., additional, Batchman, A. P., additional, Pauciulo, M. W., additional, Vidal, R., additional, Miravalle, L., additional, Goebel, H. H., additional, Cushman, L. J., additional, Azzarelli, B., additional, Horak, H., additional, Farlow, M., additional, and Nichols, W. C., additional
Published: 2005
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44. Genetic screening for a single common mutation in familial Parkinson's disease

Author: NICHOLS, W, primary, PANKRATZ, N, additional, HERNANDEZ, D, additional, PAISANRUIZ, C, additional, JAIN, S, additional, HALTER, C, additional, MICHAELS, V, additional, REED, T, additional, RUDOLPH, A, additional, and SHULTS, C, additional
Published: 2005
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45. Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families

Author: Pankratz, N., primary
Published: 2003
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46. Genes influencing Parkinson disease onset: replication of PARK3 and identification of novel loci.

Author: Pankratz N, Uniacke SK, Halter CA, Rudolph A, Shults CW, Conneally PM, Foroud T, Nichols WC, Parkinson Study Group, Pankratz, N, Uniacke, S K, Halter, C A, Rudolph, A, Shults, C W, Conneally, P M, Foroud, T, and Nichols, W C
Published: 2004
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47. Parkindosage mutations have greater pathogenicity in familial PD than simple sequence mutations

Author: Pankratz, N, Kissell, D K., Pauciulo, M W., Halter, C A., Rudolph, A, Pfeiffer, R F., Marder, K S., Foroud, T, and Nichols, W C.
Abstract: Mutations in both alleles of parkinhave been shown to result in Parkinson disease (PD). However, it is unclear whether haploinsufficiency (presence of a mutation in only 1 of the 2 parkinalleles) increases the risk for PD.
Published: 2009
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48. Variation in GIGYF2is not associated with Parkinson diseaseSYMBOL

Author: Nichols, W C., Kissell, D K., Pankratz, N, Pauciulo, M W., Elsaesser, V E., Clark, K A., Halter, C A., Rudolph, A, Wojcieszek, J, Pfeiffer, R F., and Foroud, T
Abstract: A recent study reported that mutations in a gene on chromosome 2q36-37, GIGYF2, result in Parkinson disease (PD). We have previously reported linkage to this chromosomal region in a sample of multiplex PD families, with the strongest evidence of linkage obtained using the subset of the sample having the strongest family history of disease and meeting the strictest diagnostic criteria. We have tested whether mutations in GIGYF2may account for the previously observed linkage finding.
Published: 2009
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49. Mutations in GBAare associated with familial Parkinson disease susceptibility and age at onsetSYMBOL

Author: Nichols, W C., Pankratz, N, Marek, D K., Pauciulo, M W., Elsaesser, V E., Halter, C A., Rudolph, A, Wojcieszek, J, Pfeiffer, R F., and Foroud, T
Abstract: To characterize sequence variation within the glucocerebrosidase (GBA) gene in a select subset of our sample of patients with familial Parkinson disease (PD) and then to test in our full sample whether these sequence variants increased the risk for PD and were associated with an earlier onset of disease.
Published: 2009
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50. LRRK2mutation analysis in Parkinson disease families with evidence of linkage to PARK8

Author: Nichols, W C., Elsaesser, V E., Pankratz, N, Pauciulo, M W., Marek, D K., Halter, C A., Rudolph, A, Shults, C W., and Foroud, T
Abstract: Pathogenic mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been found to cause typical, later-onset Parkinson disease (PD). Although G2019S is the most common mutation, other mutations have also been reported. It is critical to catalog the types of mutations found in LRRK2that can cause PD, so as to provide insight regarding disease susceptibility and potential novel treatments.
Published: 2007
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