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1. Emotional processing in panic disorder and its subtypes: An fMRI study using emotional faces

Author: Pattyn, T., Schmaal, L., Eede, F. Van Den, Cassiers, L., Penninx, BW, Sabbe, BCG, and Veltman, DJ
Published: 2021
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2. Charting brain growth and aging at high spatial precision

Author: Rutherford, S, Fraza, C, Dinga, R, Kia, SM, Wolfers, T, Zabihi, M, Berthet, P, Worker, A, Verdi, S, Andrews, D, Han, LK, Bayer, JM, Dazzan, P, McGuire, P, Mocking, RT, Schene, A, Sripada, C, Tso, IF, Duval, ER, Chang, S-E, Penninx, BW, Heitzeg, MM, Burt, SA, Hyde, LW, Amaral, D, Nordahl, CW, Andreasssen, OA, Westlye, LT, Zahn, R, Ruhe, HG, Beckmann, C, Marquand, AF, Rutherford, S, Fraza, C, Dinga, R, Kia, SM, Wolfers, T, Zabihi, M, Berthet, P, Worker, A, Verdi, S, Andrews, D, Han, LK, Bayer, JM, Dazzan, P, McGuire, P, Mocking, RT, Schene, A, Sripada, C, Tso, IF, Duval, ER, Chang, S-E, Penninx, BW, Heitzeg, MM, Burt, SA, Hyde, LW, Amaral, D, Nordahl, CW, Andreasssen, OA, Westlye, LT, Zahn, R, Ruhe, HG, Beckmann, C, and Marquand, AF
Abstract: Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and used normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision-making.
Published: 2022

3. The Association Between Home Stay and Symptom Severity in Major Depressive Disorder: Preliminary Findings From a Multicenter Observational Study Using Geolocation Data From Smartphones

Author: Laiou P, Kaliukhovich DA, Folarin AA, Ranjan Y, Rashid Z, Conde P, Stewart C, Sun S, Zhang Y, Matcham F, Ivan A, Lavelle G, Sara Siddi, Lamers F, Penninx BW, Haro JM, Annas P, Cummins N, Vairavan S, Manyakov NV, Narayan VA, Dobson RJ, Hotopf M, and RADAR-CNS
Abstract: BACKGROUND: Most smartphones and wearables are currently equipped with location sensing (using GPS and mobile network information), which enables continuous location tracking of their users. Several studies have reported that various mobility metrics, as well as home stay, that is, the amount of time an individual spends at home in a day, are associated with symptom severity in people with major depressive disorder (MDD). Owing to the use of small and homogeneous cohorts of participants, it is uncertain whether the findings reported in those studies generalize to a broader population of individuals with MDD symptoms.; OBJECTIVE: The objective of this study is to examine the relationship between the overall severity of depressive symptoms, as assessed by the 8-item Patient Health Questionnaire, and median daily home stay over the 2 weeks preceding the completion of a questionnaire in individuals with MDD.; METHODS: We used questionnaire and geolocation data of 164 participants with MDD collected in the observational Remote Assessment of Disease and Relapse-Major Depressive Disorder study. The participants were recruited from three study sites: King's College London in the United Kingdom (109/164, 66.5%); Vrije Universiteit Medisch Centrum in Amsterdam, the Netherlands (17/164, 10.4%); and Centro de Investigacion Biomedica en Red in Barcelona, Spain (38/164, 23.2%). We used a linear regression model and a resampling technique (n=100 draws) to investigate the relationship between home stay and the overall severity of MDD symptoms. Participant age at enrollment, gender, occupational status, and geolocation data quality metrics were included in the model as additional explanatory variables. The 95% 2-sided CIs were used to evaluate the significance of model variables.; RESULTS: Participant age and severity of MDD symptoms were found to be significantly related to home stay, with older (95% CI 0.161-0.325) and more severely affected individuals (95% CI 0.015-0.184) spending more time at home. The association between home stay and symptoms severity appeared to be stronger on weekdays (95% CI 0.023-0.178, median 0.098; home stay: 25th-75th percentiles 17.8-22.8, median 20.9 hours a day) than on weekends (95% CI -0.079 to 0.149, median 0.052; home stay: 25th-75th percentiles 19.7-23.5, median 22.3 hours a day). Furthermore, we found a significant modulation of home stay by occupational status, with employment reducing home stay (employed participants: 25th-75th percentiles 16.1-22.1, median 19.7 hours a day; unemployed participants: 25th-75th percentiles 20.4-23.5, median 22.6 hours a day).; CONCLUSIONS: Our findings suggest that home stay is associated with symptom severity in MDD and demonstrate the importance of accounting for confounding factors in future studies. In addition, they illustrate that passive sensing of individuals with depression is feasible and could provide clinically relevant information to monitor the course of illness in patients with MDD. ©Petroula Laiou, Dzmitry A Kaliukhovich, Amos A Folarin, Yatharth Ranjan, Zulqarnain Rashid, Pauline Conde, Callum Stewart, Shaoxiong Sun, Yuezhou Zhang, Faith Matcham, Alina Ivan, Grace Lavelle, Sara Siddi, Femke Lamers, Brenda WJH Penninx, Josep Maria Haro, Peter Annas, Nicholas Cummins, Srinivasan Vairavan, Nikolay V Manyakov, Vaibhav A Narayan, Richard JB Dobson, Matthew Hotopf, RADAR-CNS. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 28.01.2022.
Published: 2022

4. Relationship Between Major Depression Symptom Severity and Sleep Collected Using a Wristband Wearable Device: Multicenter Longitudinal Observational Study

Author: Zhang Y, Folarin AA, Sun S, Cummins N, Bendayan R, Ranjan Y, Rashid Z, Conde P, Stewart C, Laiou P, Matcham F, White KM, Lamers F, Sara Siddi, Simblett S, Myin-Germeys I, Rintala A, Wykes T, Haro JM, Penninx BW, Narayan VA, Hotopf M, Dobson RJ, and RADAR-CNS Consortium
Subjects: mental health, mobile health (mHealth), monitoring, sleep, wearable device, depression
Abstract: BACKGROUND: Sleep problems tend to vary according to the course of the disorder in individuals with mental health problems. Research in mental health has associated sleep pathologies with depression. However, the gold standard for sleep assessment, polysomnography (PSG), is not suitable for long-term, continuous monitoring of daily sleep, and methods such as sleep diaries rely on subjective recall, which is qualitative and inaccurate. Wearable devices, on the other hand, provide a low-cost and convenient means to monitor sleep in home settings. OBJECTIVE: The main aim of this study was to devise and extract sleep features from data collected using a wearable device and analyze their associations with depressive symptom severity and sleep quality as measured by the self-assessed Patient Health Questionnaire 8-item (PHQ-8). METHODS: Daily sleep data were collected passively by Fitbit wristband devices, and depressive symptom severity was self-reported every 2 weeks by the PHQ-8. The data used in this paper included 2812 PHQ-8 records from 368 participants recruited from 3 study sites in the Netherlands, Spain, and the United Kingdom. We extracted 18 sleep features from Fitbit data that describe participant sleep in the following 5 aspects: sleep architecture, sleep stability, sleep quality, insomnia, and hypersomnia. Linear mixed regression models were used to explore associations between sleep features and depressive symptom severity. The z score was used to evaluate the significance of the coefficient of each feature. RESULTS: We tested our models on the entire dataset and separately on the data of 3 different study sites. We identified 14 sleep features that were significantly (P
Published: 2021

5. Large-scale plasma metabolome analysis reveals alterations in HDL metabolism in migraine

Author: Onderwater, GLJ, Ligthart, L, Bot, M, Demirkan, A, Fu, J, Van Der Kallen, CJH, Vijfhuizen, LS, Pool, R, Liu, J, Vanmolkot, FHM, Beekman, M, Wen, K-X, Amin, N, Thesing, CS, Pijpers, JA, Kies, DA, Zielman, R, De Boer, I, Van Greevenbroek, MMJ, Arts, ICW, Milaneschi, Y, Schram, MT, Dagnelie, PC, Franke, L, Ikram, MA, Ferrari, MD, Goeman, JJ, Slagboom, PE, Wijmenga, C, Stehouwer, CDA, Boomsma, DI, Van Duijn, CM, Penninx, BW, Hoen, PAC, Terwindt, GM, Van Den Maagdenberg, AMJM, Consortium, Bbmri Metabolomics, Epidemiology, Neurology, Radiology & Nuclear Medicine, Interne Geneeskunde, RS: CARIM - R3 - Vascular biology, MUMC+: MA Alg Interne Geneeskunde (9), Epidemiologie, RS: FHML MaCSBio, RS: FSE MaCSBio, RS: FPN MaCSBio, MUMC+: HVC Pieken Maastricht Studie (9), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: MA Interne Geneeskunde (3), RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: CAPHRI - R5 - Optimising Patient Care, MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Reumatologie (9), APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Psychiatry, APH - Digital Health, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases
Subjects: Male, Metabolite, Proton Magnetic Resonance Spectroscopy, Pharmacology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, EPIDEMIOLOGY, 0303 health sciences, biology, GLOBAL TEST, ASSOCIATION, Middle Aged, CARDIOVASCULAR-DISEASE, Meta-analysis, Metabolome, Apolipoprotein A1, Female, Lipoproteins, HDL, Adult, medicine.medical_specialty, Migraine Disorders, BIOMARKERS, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, LIPOPROTEINS, Metabolomics, Sex Factors, SDG 3 - Good Health and Well-being, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, Nuclear Magnetic Resonance, Biomolecular, 030304 developmental biology, Aged, business.industry, medicine.disease, Confidence interval, Endocrinology, chemistry, Migraine, Metabolite profiling, biology.protein, RISK-FACTORS, Neurology (clinical), business, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], 030217 neurology & neurosurgery, Lipoprotein
Abstract: ObjectiveTo identify a plasma metabolomic biomarker signature for migraine.MethodsPlasma samples from 8 Dutch cohorts (n = 10,153: 2,800 migraine patients and 7,353 controls) were profiled on a 1H-NMR-based metabolomics platform, to quantify 146 individual metabolites (e.g., lipids, fatty acids, and lipoproteins) and 79 metabolite ratios. Metabolite measures associated with migraine were obtained after single-metabolite logistic regression combined with a random-effects meta-analysis performed in a nonstratified and sex-stratified manner. Next, a global test analysis was performed to identify sets of related metabolites associated with migraine. The Holm procedure was applied to control the family-wise error rate at 5% in single-metabolite and global test analyses.ResultsDecreases in the level of apolipoprotein A1 (β −0.10; 95% confidence interval [CI] −0.16, −0.05; adjusted p = 0.029) and free cholesterol to total lipid ratio present in small high-density lipoprotein subspecies (HDL) (β −0.10; 95% CI −0.15, −0.05; adjusted p = 0.029) were associated with migraine status. In addition, only in male participants, a decreased level of omega-3 fatty acids (β −0.24; 95% CI −0.36, −0.12; adjusted p = 0.033) was associated with migraine. Global test analysis further supported that HDL traits (but not other lipoproteins) were associated with migraine status.ConclusionsMetabolic profiling of plasma yielded alterations in HDL metabolism in migraine patients and decreased omega-3 fatty acids only in male migraineurs.
Published: 2019

6. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, SJ, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O’Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, and Giral, P
Subjects: Aging, MEGASTROKE Consortium, Quantitative Trait Loci, ADAMTS9 Protein, Coronary Disease, Cardiovascular, Polymorphism, Single Nucleotide, Carotid Intima-Media Thickness, Protein-Lysine 6-Oxidase, Risk Factors, Genetics, 2.1 Biological and endogenous factors, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Aetiology, Polymorphism, Heart Disease - Coronary Heart Disease, Plaque, Atherosclerotic, Human Genome, Single Nucleotide, Atherosclerosis, Plaque, Atherosclerotic, Brain Disorders, Stroke, Heart Disease, cardiovascular system, Amino Acid Oxidoreductases, Lod Score, Genome-Wide Association Study
Abstract: © 2018, The Author(s). Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018

7. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author: Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Maris, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pirastu, Nicola, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, McArdle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Toomas, Keis, Aime, Tammesoo, Mari-Liis, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Anders, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willems, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van Duijn, Cornelia M. McEniery CM, Wilkinson IB, Cockcroft JR, O'Shaughnessy KM, Newhouse SJ, Yasmin, Smith AV, Eiriksdottir G, Launer LJ, Sigurdsson S, Aspelund T, Gudnason V, De Bacquer D, Rietzschel ER, De Backer GG, Van Bortel L, De Buyzere ML, Segers P, Bekaert S, Gillebert TC, De Meyer T, Ferrucci L, Tanaka T, Johnson AD, Levy D, Benjamin EJ, Mitchell GF, Vita JA, Larson MG, Hamburg NM, Vasan RS, Isaacs A, Schut AF, Oostra BA, van Duijn CM, van Rijn MJ, Sie MP, Newman AB, Herrington DM, Andrews JS, Ding J, Sutton-Tyrrell KC, Harris TB, Howard TD, Liu Y, Parsa A, Shuldiner AR, McArdle PF, Gibson Q, Post WS, Dehghan A, Hofman A, Uitterlinden AG, Sijbrands EJ, Rivadeneira F, Mattace-Raso FU, Verwoert GC, Witteman JC, Scuteri A, Lakatta EG, Jewell E, Abecasis GR, Tarasov KV, Uda M, Najjar SS, Sanna S, Attwood T, Belz S, Braund P, Cambien F, Cooper J, Crisp-Hihn A, Deloukas P, Foad N, Eardman J, Goodall AH, Gracey J, Gray E, Gulde S, Gwilliams R, Heimerl S, Hengstenberg C, Jolley J, Krishnan U, Linsel-Nitschke P, Lloyd-Jones H, Lugauer I, Lundmark P, Maouche S, Moore JS, Muir D, Murray E, Nelson CP, Neudert J, Niblett D, O'Leary K, Ouwehand WH, Pollard H, Rankin A, Rice CM, Sager H, Samani NJ, Sambrook J, Schmitz G, Scholz M, Schroeder L, Schunkert H, Syvannen AC, Wallace C, Kathiresan S, Reilly MP, Erdmann J, Assimes TL, Boerwinkle E, Hall A, König IR, Laaksonen R, McPherson R, Thompson JR, Thorsteinsdottir U, Ziegler A, Absher D, Chen L, Cupples LA, Halperin E, Li M, Musunuru K, Preuss M, Schillert A, Thorleifsson G, Voight BF, Wells GA, Assime TL, Holm H, Roberts R, Stewart AF, Fortmann S, Go A, Hlatky M, Iribarren C, Knowles J, Myers R, Quertermous T, Sidney S, Risch N, Tang H, Blankenberg S, Zeller T, Wild P, Schnabel R, Sinning C, Lackner K, Tiret L, Nicaud V, Bickel C, Rupprecht HJ, Perret C, Proust C, Münzel T, Barbalic M, Bis J, Chen IY, Cupples L, Demissie-Banjaw S, Folsom A, Glazer N, Harris T, Heckbert S, Lumley T, Marciante K, Morrison A, O' Donnell CJ, Psaty BM, Rice K, Rotter JI, Siscovick DS, Smith N, Smith A, Taylor KD, van Duijn C, Volcik K, Whitteman J, Ramachandran V, Uitterlinden A, Gretarsdottir S, Gulcher JR, Kong A, Stefansson K, Thorgeirsson G, Andersen K, Fischer M, Grosshennig A, Lieb W, Stark K, Schreiber S, Wichmann HE, Aherrahrou Z, Bruse P, Doering A, Illig T, Klopp N, Loley C, Medack A, Meisinger C, Meitinger T, Nahrstedt J, Peters A, Wagner AK, Willenborg C, Böhm BO, Dobnig H, Grammer TB, Hoffmann MM, Kleber M, März W, Meinitzer A, Winkelmann BR, Pilz S, Renner W, Scharnagl H, Stojakovic T, Tomaschitz A, Winkler K, Guiducci C, Burtt N, Gabriel SB, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, Dandona S, Jarinova O, Qu L, Wilensky R, Matthai W, Hakonarson HH, Devaney J, Burnett MS, Pichard AD, Kent KM, Satler L, Lindsay JM, Waksman R, Knouff CW, Waterworth DM, Walker MC, Mooser V, Epstein SE, Rader DJ, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall AS, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Yang YA, Stricker BH, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Willerson JT, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Gao X, Yang Q, O'Connell JR, Schmidt H, Ketkar S, Hwang SJ, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria F, Metter J, de Boer IH, Siscovick D, Zillikens MC, Feitosa M, Province M, de Andrade M, Turner ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Coresh J, Schmidt R, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Felix SB, Watzinger N, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Reffelmann T, Redfield MM, Werdan K, Arnett DK, Blettner M, Friedrich N, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Vollenweider P, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JS., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), University of Leicester, Department of Genetics [Leicester], Erasmus University Rotterdam, Netherlands Genomics Initiative, Department of Epidemiology and Biostatistics, School of Public Health, Zahedan University of Medical Sciences, Washington University in Saint Louis (WUSTL), Queen Mary University of London (QMUL), National Heart, Lung and Blood Institute, Partenaires INRAE, Centre Hospitalier Universitaire Vaudois (CHUV), Université de Lausanne = University of Lausanne (UNIL), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Leiden University Medical Center (LUMC), Universiteit Leiden, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Department of Epidemiology, The Netherlands Cancer Institute, Department of Mathematics, Boston University [Boston] (BU), GlaxoSmithKline, Division of Community Health Sciences, St. George's, University of South Florida [Tampa] (USF), Universität Greifswald - University of Greifswald, University of Washington [Seattle], University of Tartu, Institute of Molecular and Cell Biology, Medical Research Council, Institut de Génomique, Centre National de Génotypage, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Medical Center Groningen, Department of Genetics, University Medical Center Groningen [Groningen] (UMCG), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Massachusetts General Hospital [Boston], Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Università degli studi di Trieste = University of Trieste, Universität zu Lübeck = University of Lübeck [Lübeck], Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, The University of Western Australia (UWA), Department of Twin Research and Genetic Epidemiology, King's College London, London, University of Oxford, Medical University Graz, National Institute on Aging, Centre for population Health Sciences, University of Edinburgh, Uppsala University, Vrije Universiteit Amsterdam [Amsterdam] (VU), Western General Hospital, Harvard Medical School [Boston] (HMS), Brigham and Women's Hospital [Boston], University of Michigan System, University of Groningen, Ealing Hospital, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Medical Genetics Institute, Cedars-Sinai Medical Center, University of Tampere, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Split, The University of Texas Health Science Center at Houston (UTHealth), Johns Hopkins University (JHU), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Swiss Institute of Bioinformatics [Lausanne] (SIB), Finnish Institute of Occupational Health, National Institute of Health and Welfare, University of Oulu, Lapland Central Hospital, University of Bristol [Bristol], Institute for Community Medicine, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), US National Institutes of Health, National Heart, Lung, and Blood Institute, European, Epidemiology, Internal Medicine, Public Health, Clinical Genetics, Université de Lausanne (UNIL), LeidenUniversity Medical Centre, University of Iceland, Università degli studi di Trieste, Universität zu Lübeck [Lübeck], University of Western Australia, University of Oxford [Oxford], VU University Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Human genetics, Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Epidemiology and Data Science, Medical Research Council (MRC), Louise V., Wain, Germaine C., Verwoert, Paul F., O'Reilly, Gang, Shi, Toby, Johnson, Andrew D., Johnson, Murielle, Bochud, Kenneth M., Rice, Peter, Henneman, Albert V., Smith, Georg B., Ehret, Najaf, Amin, Martin G., Larson, Vincent, Mooser, David, Hadley, Marcus, Dörr, Joshua C., Bi, Thor, Aspelund, Tõnu, Esko, A. Cecile J. W., Janssen, Jing Hua, Zhao, Simon, Heath, Maris, Laan, Jingyuan, Fu, Giorgio, Pisti, Jian'An, Luan, Pankaj, Arora, Gavin, Luca, Pirastu, Nicola, Irene, Pichler, Anne U., Jackson, Rebecca J., Webster, Feng, Zhang, John F., Peden, Helena, Schmidt, Toshiko, Tanaka, Harry, Campbell, Wilmar, Igl, Yuri, Milaneschi, Jouke Jan, Hottenga, Veronique, Vitart, Daniel I., Chasman, Stella, Trompet, Jennifer L., Bragg Gresham, Behrooz Z., Alizadeh, John C., Chamber, Xiuqing, Guo, Terho, Lehtimäki, Brigitte, Kühnel, Lorna M., Lopez, Ozren, Polašek, Mladen, Boban, Christopher P., Nelson, Alanna C., Morrison, Vasyl, Pihur, Santhi K., Ganesh, Albert, Hofman, Suman, Kundu, Francesco U. S., Mattace Raso, Fernando, Rivadeneira, Eric J. G., Sijbrand, Andre G., Uitterlinden, Shih Jen, Hwang, Ramachandran S., Vasan, Thomas J., Wang, Sven, Bergmann, Peter, Vollenweider, Gérard, Waeber, Jaana, Laitinen, Anneli, Pouta, Paavo, Zitting, Wendy L., Mcardle, Heyo K., Kroemer, Uwe, Völker, Henry, Völzke, Nicole L., Glazer, Kent D., Taylor, Tamara B., Harri, Helene, Alavere, Toomas, Haller, Aime, Kei, Mari Liis, Tammesoo, Yurii, Aulchenko, Inês, Barroso, Kay Tee, Khaw, Pilar, Galan, Serge, Hercberg, Mark, Lathrop, Susana, Eyheramendy, Elin, Org, Siim, Sõber, Xiaowen, Lu, Ilja M., Nolte, Brenda W., Penninx, Tanguy, Corre, Corrado, Masciullo, Cinzia, Sala, Leif, Groop, Benjamin F., Voight, Olle, Melander, Christopher J., O'Donnell, Veikko, Salomaa, D'Adamo, ADAMO PIO, Antonella, Fabretto, Flavio, Faletra, Sheila, Ulivi, Fabiola Del Greco, M, Maurizio, Facheri, Francis S., Collin, Richard N., Bergman, John P., Beilby, Joseph, Hung, A., William Musk, Massimo, Mangino, So Youn, Shin, Nicole, Soranzo, Hugh, Watkin, Anuj, Goel, Anders, Hamsten, Pierre, Gider, Marisa, Loitfelder, Marion, Zeginigg, Dena, Hernandez, Samer S., Najjar, Pau, Navarro, Sarah H., Wild, Anna Maria, Corsi, Andrew, Singleton, Eco J. C., de Geu, Gonneke, Willemsen, Alex N., Parker, Lynda M., Rose, Brendan, Buckley, David, Stott, Marco, Orru, Manuela, Uda, Melanie M., van der Klauw, Weihua, Zhang, Xinzhong, Li, James, Scott, Yii Der Ida, Chen, Gregory L., Burke, Mika, Kähönen, Jorma, Viikari, Angela, Döring, Thomas, Meitinger, Gail, Davie, John M., Starr, Valur, Emilsson, Andrew, Plump, Jan H., Lindeman, Peter A. C., 't Hoen, Inke R., König, Janine F., Felix, Robert, Clarke, Jemma C., Hopewell, Halit, Ongen, Monique, Breteler, Stéphanie, Debette, Anita L., Destefano, Myriam, Fornage, Gary F., Mitchell, Nicholas L., Smith, Hilma, Holm, Kari, Stefansson, Gudmar, Thorleifsson, Unnur, Thorsteinsdottir, Nilesh J., Samani, Michael, Preu, Igor, Rudan, Caroline, Hayward, Ian J., Deary, H., Erich Wichmann, Olli T., Raitakari, Walter, Palma, Jaspal S., Kooner, Ronald P., Stolk, J., Wouter Jukema, Alan F., Wright, Dorret I., Boomsma, Stefania, Bandinelli, Ulf B., Gyllensten, James F., Wilson, Luigi, Ferrucci, Reinhold, Schmidt, Martin, Farrall, Tim D., Spector, Lyle J., Palmer, Jaakko, Tuomilehto, Arne, Pfeufer, Gasparini, Paolo, David, Siscovick, David, Altshuler, Ruth J. F., Loo, Daniela, Toniolo, Harold, Snieder, Christian, Gieger, Pierre, Meneton, Nicholas J., Wareham, Ben A., Oostra, Andres, Metspalu, Lenore, Launer, Rainer, Rettig, David P., Strachan, Jacques S., Beckmann, Jacqueline C. M., Witteman, Jeanette, Erdmann, Ko Willems van, Dijk, Eric, Boerwinkle, Michael, Boehnke, Paul M., Ridker, Marjo Riitta, Jarvelin, Aravinda, Chakravarti, Goncalo R., Abecasi, Vilmundur, Gudnason, Christopher Newton, Cheh, Daniel, Levy, Patricia B., Munroe, Bruce M., Psaty, Mark J., Caulfield, Dabeeru C., Rao, Martin D., Tobin, Paul, Elliott, Cornelia M., van Duijn, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcu, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Mari, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, Mcardle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Tooma, Keis, Aime, Tammesoo, Mari-Lii, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Ander, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, Jame, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thoma, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andre, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willem, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van, Duijn, Cornelia M., McEniery CM, Wilkinson, Ib, Cockcroft, Jr, O'Shaughnessy, Km, Newhouse, Sj, Yasmin, Smith, Av, Eiriksdottir, G, Launer, Lj, Sigurdsson, S, Aspelund, T, Gudnason, V, De Bacquer, D, Rietzschel, Er, De Backer, Gg, Van Bortel, L, De Buyzere, Ml, Segers, P, Bekaert, S, Gillebert, Tc, De Meyer, T, Ferrucci, L, Tanaka, T, Johnson, Ad, Levy, D, Benjamin, Ej, Mitchell, Gf, Vita, Ja, Larson, Mg, Hamburg, Nm, Vasan, R, Isaacs, A, Schut, Af, Oostra, Ba, van Duijn, Cm, van Rijn, Mj, Sie, Mp, Newman, Ab, Herrington, Dm, Andrews, J, Ding, J, Sutton-Tyrrell, Kc, Harris, Tb, Howard, Td, Liu, Y, Parsa, A, Shuldiner, Ar, Mcardle, Pf, Gibson, Q, Post, W, Dehghan, A, Hofman, A, Uitterlinden, Ag, Sijbrands, Ej, Rivadeneira, F, Mattace-Raso, Fu, Verwoert, Gc, Witteman, Jc, Scuteri, A, Lakatta, Eg, Jewell, E, Abecasis, Gr, Tarasov, Kv, Uda, M, Najjar, S, Sanna, S, Attwood, T, Belz, S, Braund, P, Cambien, F, Cooper, J, Crisp-Hihn, A, Deloukas, P, Foad, N, Eardman, J, Goodall, Ah, Gracey, J, Gray, E, Gulde, S, Gwilliams, R, Heimerl, S, Hengstenberg, C, Jolley, J, Krishnan, U, Linsel-Nitschke, P, Lloyd-Jones, H, Lugauer, I, Lundmark, P, Maouche, S, Moore, J, Muir, D, Murray, E, Nelson, Cp, Neudert, J, Niblett, D, O'Leary, K, Ouwehand, Wh, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Samani, Nj, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Schunkert, H, Syvannen, Ac, Wallace, C, Kathiresan, S, Reilly, Mp, Erdmann, J, Assimes, Tl, Boerwinkle, E, Hall, A, König, Ir, Laaksonen, R, Mcpherson, R, Thompson, Jr, Thorsteinsdottir, U, Ziegler, A, Absher, D, Chen, L, Cupples, La, Halperin, E, Li, M, Musunuru, K, Preuss, M, Schillert, A, Thorleifsson, G, Voight, Bf, Wells, Ga, Assime, Tl, Holm, H, Roberts, R, Stewart, Af, Fortmann, S, Go, A, Hlatky, M, Iribarren, C, Knowles, J, Myers, R, Quertermous, T, Sidney, S, Risch, N, Tang, H, Blankenberg, S, Zeller, T, Wild, P, Schnabel, R, Sinning, C, Lackner, K, Tiret, L, Nicaud, V, Bickel, C, Rupprecht, Hj, Perret, C, Proust, C, Münzel, T, Barbalic, M, Bis, J, Chen, Iy, Cupples, L, Demissie-Banjaw, S, Folsom, A, Glazer, N, Harris, T, Heckbert, S, Lumley, T, Marciante, K, Morrison, A, O' Donnell, Cj, Psaty, Bm, Rice, K, Rotter, Ji, Siscovick, D, Smith, N, Smith, A, Taylor, Kd, van Duijn, C, Volcik, K, Whitteman, J, Ramachandran, V, Uitterlinden, A, Gretarsdottir, S, Gulcher, Jr, Kong, A, Stefansson, K, Thorgeirsson, G, Andersen, K, Fischer, M, Grosshennig, A, Lieb, W, Stark, K, Schreiber, S, Wichmann, He, Aherrahrou, Z, Bruse, P, Doering, A, Illig, T, Klopp, N, Loley, C, Medack, A, Meisinger, C, Meitinger, T, Nahrstedt, J, Peters, A, Wagner, Ak, Willenborg, C, Böhm, Bo, Dobnig, H, Grammer, Tb, Hoffmann, Mm, Kleber, M, März, W, Meinitzer, A, Winkelmann, Br, Pilz, S, Renner, W, Scharnagl, H, Stojakovic, T, Tomaschitz, A, Winkler, K, Guiducci, C, Burtt, N, Gabriel, Sb, O'Donnell, Cj, Elosua, R, Peltonen, L, Salomaa, V, Schwartz, Sm, Melander, O, Altshuler, D, Dandona, S, Jarinova, O, Qu, L, Wilensky, R, Matthai, W, Hakonarson, Hh, Devaney, J, Burnett, M, Pichard, Ad, Kent, Km, Satler, L, Lindsay, Jm, Waksman, R, Knouff, Cw, Waterworth, Dm, Walker, Mc, Mooser, V, Epstein, Se, Rader, Dj, Wright, Bj, Balmforth, Aj, Ball, Sg, Smith, Nl, Felix, Jf, Morrison, Ac, Demissie, S, Glazer, Nl, Loehr, Lr, Rosamond, Wd, Bis, Jc, Folsom, Ar, Benjamin, E, Aulchenko, Y, Haritunians, T, Couper, D, Murabito, J, Yang, Ya, Stricker, Bh, Gottdiener, J, Chang, Pp, Wang, Tj, Rice, Km, Heckbert, Sr, Fox, Er, Willerson, Jt, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Gao, X, Yang, Q, O'Connell, Jr, Schmidt, H, Ketkar, S, Hwang, Sj, Teumer, A, Paré, G, Atkinson, Ej, Lohman, K, Cornelis, Mc, Probst-Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Rampersaud, E, Mitchell, Bd, Arking, De, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer, Ih, Zillikens, Mc, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, A, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W, Coresh, J, Schmidt, R, Shlipak, Mg, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Felix, Sb, Watzinger, N, Homuth, G, Aragam, J, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, Rj, Greiser, Kh, Deckers, Jw, Stritzke, J, Lackner, Kj, Ingelsson, E, Kullo, I, Haerting, J, Reffelmann, T, Redfield, Mm, Werdan, K, Arnett, Dk, Blettner, M, Friedrich, N, Chambers, Jc, Zhang, W, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Davey Smith, G, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, Homan van der Heide, Jj, Hepkema, Bg, Hernandez-Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Munroe, Pb, Nordfors, L, Penninx, Bw, Perucha, E, Pouta, A, Roderick, Pj, Ruokonen, A, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Vollenweider, P, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Lightstone, L, Scott, J, Navis, G, Elliott, P, and Kooner, Js.
Subjects: Netherlands Twin Register (NTR), Linkage disequilibrium, pulse pressure, mean arterial pressure, genome-wide, [SDV]Life Sciences [q-bio], Genome-wide association study, BLOOD-PRESSURE, Blood Pressure, 030204 cardiovascular system & hematology, Linkage Disequilibrium, 0302 clinical medicine, RELEVANCE, CardioGram, Medicine and Health Sciences, Genetics & Heredity, ddc:616, Genetics, 0303 health sciences, Genome-wide association, 11 Medical And Health Sciences, Arteries, ADRENERGIC-RECEPTOR TRAFFICKING, Pulse pressure, EchoGen consortium, Hypertension, HEART-FAILURE, arterial pressure, Case-Control Studie, Life Sciences & Biomedicine, Human, circulatory and respiratory physiology, medicine.medical_specialty, Mean arterial pressure, Arterie, AortaGen Consortium, Cardiogenics consortium, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, METAANALYSIS, 030304 developmental biology, Genetic association, Science & Technology, HYPERTENSION, MORTALITY, Case-control study, CARDIOVASCULAR-DISEASE RISK, 06 Biological Sciences, GENE, MICE, Endocrinology, Blood pressure, CKDGen consortium, Genetic Loci, Case-Control Studies, KidneyGen consortium, CHARGE Consortium Heart Failure Working Group, LifeLines Cohort Study, Developmental Biology, Follow-Up Studies, Genome-Wide Association Study
Abstract: Les affiliations des 100 premiers auteurs sont renseignées dans la notice. Les affiliations des autres auteurs sont disponibles à la fin de la publication.; International audience; Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
Published: 2016

8. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Author: Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'an, Arora, Pankaj, Dehghan, Abbas, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, McArdle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Dreisbach, Albert W., Li, Yali, Hunter Young, J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthias, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johannes, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inês, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Sun, Yan V., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Markus, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margus, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, McKenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thomas, Wichmann, H. -Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, James, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J., Schwartz, Stephen M., Arfan Ikram, M., Longstreth Jr. , W. T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Anders, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcus, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Panos, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Janos, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charles, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Maris, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang H, Knowles J, Hlatky M, Fortmann S, Assimes TL, Quertermous T, Go A, Iribarren C, Absher D, Risch N, Meyers R, Sidney S, Ziegler A, Schillert A, Bickel C, Sinning C, Rupprecht HJ, Lackner K, Wild P, Schnabel R, Blankenberg S, Zeller T, Münzel T, Perret C, Cambien F, Tiret L, Nicaud V, Proust C, Dehghan A, Hofman A, Uitterlinden A, van Duijn C, Levy D, Whitteman J, Cupples LA, Demissie-Banjaw S, Ramachandran V, Smith A, Gudnason V, Boerwinkle E, Folsom A, Morrison A, Psaty BM, Chen IY, Rotter JI, Bis J, Volcik K, Rice K, Taylor KD, Marciante K, Smith N, Glazer N, Heckbert S, Harris T, Lumley T, Kong A, Thorleifsson G, Thorgeirsson G, Holm H, Gulcher JR, Stefansson K, Andersen K, Gretarsdottir S, Thorsteinsdottir U, Preuss M, Schreiber S, Meitinger T, König IR, Lieb W, Hengstenberg C, Schunkert H, Erdmann J, Fisher M, Grosshennig A, Medack A, Stark K, Linsel-Nitschke P, Bruse P, Aherrahrou Z, Peters A, Loley C, Willenborg C, Nahrstedt J, Freyer J, Gulde S, Doering A, Meisinger C, Wichmann HE, Klopp N, Illig T, Meinitzer A, Tomaschitz A, Halperin E, Dobnig H, Scharnagl H, Kleber M, Laaksonen R, Pilz S, Grammer TB, Stojakovic T, Renner W, März W, Böhm BO, Winkelmann BR, Winkler K, Hoffmann M, O'Donnell CJ, Voight BF, Altshuler D, Siscovick DS, Musunuru K, Peltonen L, Barbalic M, Melander O, Elosua R, Kathiresan S, Schwartz SM, Salomaa V, Guiducci C, Burtt N, Gabriel SB, Stewart AF, Wells GA, Chen L, Jarinova O, Roberts R, McPherson R, Dandona S, Pichard AD, Rader DJ, Devaney J, Lindsay JM, Kent KM, Qu L, Satler L, Burnett MS, Li M, Reilly MP, Wilensky R, Waksman R, Epstein S, Mattha W, Knouf CW, Waterworth DM, Hakonarson HH, Walker M, Mooser V, Hall AS, Balmforth AJ, Wright BJ, Nelson C, Thompson JR, Samani NJ, Braund PS, Ball SG, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Rivadeneira F, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Wang YA, Stricker B, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Uitterlinden AG, Willerson JT, van Duijn CM, Witteman JC, Vasan RS, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Parsa A, Gao X, Yang Q, Smith AV, O'Connell JR, Schmidt H, Tanaka T, Isaacs A, Ketkar S, Hwang SJ, Johnson A, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Aspelund T, Eiriksdottir G, Launer LJ, Harris TB, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria, Francesco, Metter J, de Boer J, Siscovick D, Zillikens MC, Oostra BA, Feitosa M, Province M, de Andrade M, Turne ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Liu Y, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Shuldiner AR, Coresh J, Schmidt R, Ferrucci L, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Vasan R, Felix SB, Watzinger N, Larson MG, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Stricker BH, Reffelmann T, Redfield MM, Werdan K, Mitchell GF, Arnett D, Blettner M, Friedrich N, Benjamin EJ, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic T, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Sanna S, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Uda M, Vollenweider P, Wallace C, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Abecasis GR, Lightstone L, Scott J, Navis G, Elliot P, Kooner JS., AII - Amsterdam institute for Infection and Immunity, Nephrology, Epidemiologie, RS: CARIM School for Cardiovascular Diseases, Epidemiology, Medical Microbiology & Infectious Diseases, Radiology & Nuclear Medicine, Cardiology, Internal Medicine, Clinical Genetics, Erasmus MC other, Obstetrics & Gynecology, International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium, Zhao, Jing Hua [0000-0003-4930-3582], Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Khaw, Kay-Tee [0000-0002-8802-2903], Danesh, John [0000-0003-1158-6791], Soranzo, Nicole [0000-0003-1095-3852], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Center for Complex Disease Genomics, Johns Hopkins University School of Medicine, Clinical Pharmacology and The Genome Centre, Queen Mary University of London (QMUL), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Center for Human Genetic Research, Massachusetts General Hospital [Boston], Program in Medical and Population Genetics, Harvard University-Massachusetts Institute of Technology (MIT), Ehret, Georg B., Munroe, Patricia B., Rice, Kenneth M., Bochud, Murielle, Johnson, Andrew D., Chasman, Daniel I., Smith, Albert V., Tobin, Martin D., Verwoert, Germaine C., Hwang, Shih-Jen, Pihur, Vasyl, Vollenweider, Peter, O'Reilly, Paul F., Amin, Najaf, Bragg-Gresham, Jennifer L., Teumer, Alexander, Glazer, Nicole L., Launer, Lenore, Zhao, Jing Hua, Aulchenko, Yurii, Heath, Simon, Sober, Siim, Parsa, Afshin, Luan, Jian'An, Arora, Pankaj, Dehghan, Abba, Zhang, Feng, Lucas, Gavin, Hicks, Andrew A., Jackson, Anne U., Peden, John F., Tanaka, Toshiko, Wild, Sarah H., Rudan, Igor, Igl, Wilmar, Milaneschi, Yuri, Parker, Alex N., Fava, Cristiano, Chambers, John C., Fox, Ervin R., Kumari, Meena, Go, Min Jin, van der Harst, Pim, Kao, Wen Hong Linda, Sjögren, Marketa, Vinay, D. G., Alexander, Myriam, Tabara, Yasuharu, Shaw-Hawkins, Sue, Whincup, Peter H., Liu, Yongmei, Shi, Gang, Kuusisto, Johanna, Tayo, Bamidele, Seielstad, Mark, Sim, Xueling, Hoang Nguyen, Khanh-Dung, Lehtimäki, Terho, Matullo, Giuseppe, Wu, Ying, Gaunt, Tom R., Charlotte Onland-Moret, N., Cooper, Matthew N., Platou, Carl G. P., Org, Elin, Hardy, Rebecca, Dahgam, Santosh, Palmen, Jutta, Vitart, Veronique, Braund, Peter S., Kuznetsova, Tatiana, Uiterwaal, Cuno S. P. M., Adeyemo, Adebowale, Palmas, Walter, Campbell, Harry, Ludwig, Barbara, Tomaszewski, Maciej, Tzoulaki, Ioanna, Palmer, Nicholette D., Aspelund, Thor, Garcia, Melissa, Chang, Yen-Pei C., O'Connell, Jeffrey R., Steinle, Nanette I., Grobbee, Diederick E., Arking, Dan E., Kardia, Sharon L., Morrison, Alanna C., Hernandez, Dena, Najjar, Samer, Mcardle, Wendy L., Hadley, David, Brown, Morris J., Connell, John M., Hingorani, Aroon D., Day, Ian N. M., Lawlor, Debbie A., Beilby, John P., Lawrence, Robert W., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Dreisbach, Albert W., Li, Yali, Hunter Young, J., Bis, Joshua C., Kähönen, Mika, Viikari, Jorma, Adair, Linda S., Lee, Nanette R., Chen, Ming-Huei, Olden, Matthia, Pattaro, Cristian, Bolton, Judith A Hoffman, Köttgen, Anna, Bergmann, Sven, Mooser, Vincent, Chaturvedi, Nish, Frayling, Timothy M., Islam, Muhammad, Jafar, Tazeen H., Erdmann, Jeanette, Kulkarni, Smita R., Bornstein, Stefan R., Grässler, Jürgen, Groop, Leif, Voight, Benjamin F., Kettunen, Johanne, Howard, Philip, Taylor, Andrew, Guarrera, Simonetta, Ricceri, Fulvio, Emilsson, Valur, Plump, Andrew, Barroso, Inê, Khaw, Kay-Tee, Weder, Alan B., Hunt, Steven C., Sun, Yan V., Bergman, Richard N., Collins, Francis S., Bonnycastle, Lori L., Scott, Laura J., Stringham, Heather M., Peltonen, Leena, Perola, Marku, Vartiainen, Erkki, Brand, Stefan-Martin, Staessen, Jan A., Wang, Thomas J., Burton, Paul R., Artigas, Maria Soler, Dong, Yanbin, Snieder, Harold, Wang, Xiaoling, Zhu, Haidong, Lohman, Kurt K., Rudock, Megan E., Heckbert, Susan R., Smith, Nicholas L., Wiggins, Kerri L., Doumatey, Ayo, Shriner, Daniel, Veldre, Gudrun, Viigimaa, Margu, Kinra, Sanjay, Prabhakaran, Dorairaj, Tripathy, Vikal, Langefeld, Carl D., Rosengren, Annika, Thelle, Dag S., Corsi, Anna Maria, Singleton, Andrew, Forrester, Terrence, Hilton, Gina, Mckenzie, Colin A., Salako, Tunde, Iwai, Naoharu, Kita, Yoshikuni, Ogihara, Toshio, Ohkubo, Takayoshi, Okamura, Tomonori, Ueshima, Hirotsugu, Umemura, Satoshi, Eyheramendy, Susana, Meitinger, Thoma, Wichmann, H. -Erich, Cho, Yoon Shin, Kim, Hyung-Lae, Lee, Jong-Young, Scott, Jame, Sehmi, Joban S., Zhang, Weihua, Hedblad, Bo, Nilsson, Peter, Smith, George Davey, Wong, Andrew, Narisu, Narisu, Stančáková, Alena, Raffel, Leslie J., Yao, Jie, Kathiresan, Sekar, O'Donnell, Christopher J., Schwartz, Stephen M., Arfan Ikram, M., Longstreth Jr., W. T., Mosley, Thomas H., Seshadri, Sudha, Shrine, Nick R. G., Wain, Louise V., Morken, Mario A., Swift, Amy J., Laitinen, Jaana, Prokopenko, Inga, Zitting, Paavo, Cooper, Jackie A., Humphries, Steve E., Danesh, John, Rasheed, Asif, Goel, Anuj, Hamsten, Ander, Watkins, Hugh, Bakker, Stephan J. L., van Gilst, Wiek H., Janipalli, Charles S., Radha Mani, K., Yajnik, Chittaranjan S., Hofman, Albert, Mattace-Raso, Francesco U. S., Oostra, Ben A., Demirkan, Ayse, Isaacs, Aaron, Rivadeneira, Fernando, Lakatta, Edward G., Orru, Marco, Scuteri, Angelo, Ala-Korpela, Mika, Kangas, Antti J., Lyytikäinen, Leo-Pekka, Soininen, Pasi, Tukiainen, Taru, Würtz, Peter, Twee-HeeOng, Rick, Dörr, Marcu, Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Zelenika, Diana, Deloukas, Pano, Mangino, Massimo, Spector, Tim D., Zhai, Guangju, Meschia, James F., Nalls, Michael A., Sharma, Pankaj, Terzic, Jano, Kranthi Kumar, M. V., Denniff, Matthew, Zukowska-Szczechowska, Ewa, Wagenknecht, Lynne E., Fowkes, F. Gerald R., Charchar, Fadi J., Schwarz, Peter E. H., Hayward, Caroline, Guo, Xiuqing, Rotimi, Charle, Bots, Michiel L., Brand, Eva, Samani, Nilesh J., Polasek, Ozren, Talmud, Philippa J., Nyberg, Fredrik, Kuh, Diana, Laan, Mari, Hveem, Kristian, Palmer, Lyle J., van der Schouw, Yvonne T., Casas, Juan P., Mohlke, Karen L., Vineis, Paolo, Raitakari, Olli, Ganesh, Santhi K., Wong, Tien Y., Shyong Tai, E., Cooper, Richard S., Laakso, Markku, Rao, Dabeeru C., Harris, Tamara B., Morris, Richard W., Dominiczak, Anna F., Kivimaki, Mika, Marmot, Michael G., Miki, Tetsuro, Saleheen, Danish, Chandak, Giriraj R., Coresh, Josef, Navis, Gerjan, Salomaa, Veikko, Han, Bok-Ghee, Zhu, Xiaofeng, Kooner, Jaspal S., Melander, Olle, Ridker, Paul M., Bandinelli, Stefania, Gyllensten, Ulf B., Wright, Alan F., Wilson, James F., Ferrucci, Luigi, Farrall, Martin, Tuomilehto, Jaakko, Pramstaller, Peter P., Elosua, Roberto, Soranzo, Nicole, Sijbrands, Eric J. G., Altshuler, David, Loos, Ruth J. F., Shuldiner, Alan R., Gieger, Christian, Meneton, Pierre, Uitterlinden, Andre G., Wareham, Nicholas J., Gudnason, Vilmundur, Rotter, Jerome I., Rettig, Rainer, Uda, Manuela, Strachan, David P., Witteman, Jacqueline C. M., Hartikainen, Anna-Liisa, Beckmann, Jacques S., Boerwinkle, Eric, Vasan, Ramachandran S., Boehnke, Michael, Larson, Martin G., Järvelin, Marjo-Riitta, Psaty, Bruce M., Abecasis, Gonçalo R., Chakravarti, Aravinda, Elliott, Paul, van Duijn, Cornelia M., Newton-Cheh, Christopher, Levy, Daniel, Caulfield, Mark J., Johnson, Toby, Tang, H, Knowles, J, Hlatky, M, Fortmann, S, Assimes, Tl, Quertermous, T, Go, A, Iribarren, C, Absher, D, Risch, N, Meyers, R, Sidney, S, Ziegler, A, Schillert, A, Bickel, C, Sinning, C, Rupprecht, Hj, Lackner, K, Wild, P, Schnabel, R, Blankenberg, S, Zeller, T, Münzel, T, Perret, C, Cambien, F, Tiret, L, Nicaud, V, Proust, C, Dehghan, A, Hofman, A, Uitterlinden, A, van Duijn, C, Levy, D, Whitteman, J, Cupples, La, Demissie-Banjaw, S, Ramachandran, V, Smith, A, Gudnason, V, Boerwinkle, E, Folsom, A, Morrison, A, Psaty, Bm, Chen, Iy, Rotter, Ji, Bis, J, Volcik, K, Rice, K, Taylor, Kd, Marciante, K, Smith, N, Glazer, N, Heckbert, S, Harris, T, Lumley, T, Kong, A, Thorleifsson, G, Thorgeirsson, G, Holm, H, Gulcher, Jr, Stefansson, K, Andersen, K, Gretarsdottir, S, Thorsteinsdottir, U, Preuss, M, Schreiber, S, Meitinger, T, König, Ir, Lieb, W, Hengstenberg, C, Schunkert, H, Erdmann, J, Fisher, M, Grosshennig, A, Medack, A, Stark, K, Linsel-Nitschke, P, Bruse, P, Aherrahrou, Z, Peters, A, Loley, C, Willenborg, C, Nahrstedt, J, Freyer, J, Gulde, S, Doering, A, Meisinger, C, Wichmann, He, Klopp, N, Illig, T, Meinitzer, A, Tomaschitz, A, Halperin, E, Dobnig, H, Scharnagl, H, Kleber, M, Laaksonen, R, Pilz, S, Grammer, Tb, Stojakovic, T, Renner, W, März, W, Böhm, Bo, Winkelmann, Br, Winkler, K, Hoffmann, M, O'Donnell, Cj, Voight, Bf, Altshuler, D, Siscovick, D, Musunuru, K, Peltonen, L, Barbalic, M, Melander, O, Elosua, R, Kathiresan, S, Schwartz, Sm, Salomaa, V, Guiducci, C, Burtt, N, Gabriel, Sb, Stewart, Af, Wells, Ga, Chen, L, Jarinova, O, Roberts, R, Mcpherson, R, Dandona, S, Pichard, Ad, Rader, Dj, Devaney, J, Lindsay, Jm, Kent, Km, Qu, L, Satler, L, Burnett, M, Li, M, Reilly, Mp, Wilensky, R, Waksman, R, Epstein, S, Mattha, W, Knouf, Cw, Waterworth, Dm, Hakonarson, Hh, Walker, M, Mooser, V, Hall, A, Balmforth, Aj, Wright, Bj, Nelson, C, Thompson, Jr, Samani, Nj, Braund, P, Ball, Sg, Smith, Nl, Felix, Jf, Morrison, Ac, Demissie, S, Glazer, Nl, Loehr, Lr, Rosamond, Wd, Rivadeneira, F, Bis, Jc, Folsom, Ar, Benjamin, E, Aulchenko, Y, Haritunians, T, Couper, D, Murabito, J, Wang, Ya, Stricker, B, Gottdiener, J, Chang, Pp, Wang, Tj, Rice, Km, Heckbert, Sr, Fox, Er, Uitterlinden, Ag, Willerson, Jt, van Duijn, Cm, Witteman, Jc, Vasan, R, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Parsa, A, Gao, X, Yang, Q, Smith, Av, O'Connell, Jr, Schmidt, H, Tanaka, T, Isaacs, A, Ketkar, S, Hwang, Sj, Johnson, A, Teumer, A, Paré, G, Atkinson, Ej, Lohman, K, Cornelis, Mc, Probst-Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, Lj, Harris, Tb, Rampersaud, E, Mitchell, Bd, Arking, De, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, Francesco, Metter, J, de Boer, J, Zillikens, Mc, Oostra, Ba, Feitosa, M, Province, M, de Andrade, M, Turne, St, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, A, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Liu, Y, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W, Shuldiner, Ar, Coresh, J, Schmidt, R, Ferrucci, L, Shlipak, Mg, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Felix, Sb, Watzinger, N, Larson, Mg, Homuth, G, Aragam, J, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, Rj, Greiser, Kh, Deckers, Jw, Stritzke, J, Lackner, Kj, Ingelsson, E, Kullo, I, Haerting, J, Stricker, Bh, Reffelmann, T, Redfield, Mm, Werdan, K, Mitchell, Gf, Arnett, D, Blettner, M, Friedrich, N, Benjamin, Ej, Chambers, Jc, Zhang, W, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Davey Smith, G, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, T, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, Homan van der Heide, Jj, Hepkema, Bg, Hernandez-Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Munroe, Pb, Nordfors, L, Penninx, Bw, Perucha, E, Pouta, A, Roderick, Pj, Ruokonen, A, Sanna, S, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliot, P, and Kooner, Js.
Subjects: novel loci, Kidney Disease, Polymorphism, Single Nucleotide/*genetics, [SDV]Life Sciences [q-bio], left ventricular wall thickness, LOCI, Genome-wide association study, Blood Pressure, Disease, Coronary Artery Disease, 030204 cardiovascular system & hematology, Coronary artery disease, 0302 clinical medicine, RELEVANCE, Africa/ethnology, Cardiovascular Disease, genetics, Kidney Diseases/genetics, Stroke, genome wide association study, POPULATION, ta118, Blood pressure, hypertension, stroke, coronary artery disease, ddc:616, 0303 health sciences, education.field_of_study, Asia/ethnology, Multidisciplinary, Coronary Artery Disease/genetics, COMMON VARIANTS, Genetic Predisposition to Disease/*genetics, 3. Good health, Europe, Cardiovascular Diseases, Hypertension, Cardiology, Kidney Diseases, HEALTH, Human, medicine.medical_specialty, Asia, Population, Renal function, Polymorphism, Single Nucleotide, Europe/ethnology, Article, CLONING, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Stroke/genetics, Internal medicine, medicine, Humans, Cardiovascular Diseases/*genetics, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, METAANALYSIS, 030304 developmental biology, RECEPTOR, genes, blood pressure, cardiovascular disease risk, medicine.disease, Africa, Blood Pressure/*genetics/physiology, Hypertension/genetics, Kidney disease, Genome-Wide Association Study
Abstract: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. ispartof: Nature vol:478 issue:7367 pages:103-109 ispartof: location:England status: published
Published: 2011

9. Genome-wide meta-analysis identifies new susceptibility loci for migraine

Author: Anttila V, Winsvold BS, Gormley P, Kurth T, Bettella F, McMahon G, Kallela M, Malik R, de Vries B, Terwindt G, Medland SE, Todt U, McArdle WL, Quaye L, Koiranen M, Ligthart L, Hottenga JJ, Vink JM, Penninx BW, Boomsma DI, Strachan DP, Kubisch C, Ferrari MD, van den Maagdenberg AM, Dichgans M, Wessman M, Smith GD, Stefansson K, Daly MJ, Nyholt DR, Chasman DI, Palotie A, North American Brain Expression Consortium, UK Brain Expression Consortium, International Headache Genetics Consortium, Anttila V, Winsvold BS, Gormley P, Kurth T, Bettella F, McMahon G, Kallela M, Malik R, de Vries B, Terwindt G, Medland SE, Todt U, McArdle WL, Quaye L, Koiranen M, Ligthart L, Hottenga JJ, Vink JM, Penninx BW, Boomsma DI, Strachan DP, Kubisch C, Ferrari MD, van den Maagdenberg AM, Dichgans M, Wessman M, Smith GD, Stefansson K, Daly MJ, Nyholt DR, Chasman DI, and Palotie A
Published: 2013

10. Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans

Author: Huffman, JE, Albrecht, E, Teumer, A, Mangino, M, Kapur, K, Johnson, T, Kutalik, Z, Pirastu, N, Pistis, G, Lopez, LM, Haller, T, Salo, P, Goel, A, Li, M, Tanaka, T, Dehghan, Abbas, Ruggiero, D, Malerba, G, Smith, AV, Nolte, IM (Ilja), Portas, L, Phipps-Green, A, Boteva, L, Navarro, P, Johansson, A, Hicks, AA, Polasek, O, Esko, T, Peden, JF, Harris, SE, Murgia, F, Wild, SH, Tenesa, A, Tin, A, Mihailov, E, Grotevendt, A, Gislason, GK, Coresh, J, d'Adamo, P, Ulivi, S, Vollenweider, P, Waeber, G, Campbell, S, Kolcic, I, Fisher, K, Viigimaa, M, Metter, JE, Masciullo, C, Trabetti, E, Bombieri, C, Sorice, R, Doring, A, Reischl, E, Strauch, K, Hofman, Bert, Uitterlinden, André, Waldenberger, M, Wichmann, HE, Davies, G, Gow, AJ, Dalbeth, N, Stamp, L, Smit, JH, Kirin, M, Nagaraja, R, Nauck, M, Schurmann, C, Budde, K, Farrington, SM, Theodoratou, E, Jula, A, Salomaa, V, Sala, C, Hengstenberg, C, Burnier, M, Magi, R, Klopp, N, Kloiber, S, Schipf, S, Ripatti, S, Cabras, S, Soranzo, N, Homuth, G, Nutile, T, Munroe, PB, Hastie, N, Campbell, H, Rudan, I, Cabrera, C, Haley, C, Franco Duran, OH, Merriman, TR, Gudnason, V, Pirastu, M, Penninx, BW, Snieder, H, Metspalu, A, Ciullo, M, Pramstaller, PP, Duijn, Cornelia, Ferrucci, L, Gambaro, G, Deary, IJ, Dunlop, MG, Wilson, JF, Gasparini, P, Gyllensten, U, Spector, TD, Wright, AF, Hayward, C, Watkins, H, Perola, M, Bochud, M, Kao, WHL, Caulfield, M, Toniolo, D, Volzke, H, Gieger, C, Kottgen, A, Vitart, V, Huffman, Jennifer E., Albrecht, Eva, Teumer, Alexander, Mangino, Massimo, Kapur, Karen, Johnson, Toby, Kutalik, Zoltán, Pirastu, Nicola, Pistis, Giorgio, Lopez, Lorna M., Haller, Tooma, Salo, Perttu, Goel, Anuj, Li, Man, Tanaka, Toshiko, Dehghan, Abba, Ruggiero, Daniela, Malerba, Giovanni, Smith, Albert V., Nolte, Ilja M., Portas, Laura, Phipps Green, Amanda, Boteva, Lora, Navarro, Pau, Johansson, Asa, Hicks, Andrew A., Polasek, Ozren, Esko, Tõnu, Peden, John F., Harris, Sarah E., Murgia, Federico, Wild, Sarah H., Tenesa, Albert, Tin, Adrienne, Mihailov, Evelin, Grotevendt, Anne, Gislason, Gauti K., Coresh, Josef, D'Adamo, ADAMO PIO, Ulivi, Sheila, Vollenweider, Peter, Waeber, Gerard, Campbell, Susan, Kolcic, Ivana, Fisher, Krista, Viigimaa, Margu, Metter, Jeffrey E., Masciullo, Corrado, Trabetti, Elisabetta, Bombieri, Cristina, Sorice, Rossella, Döring, Angela, Reischl, Eva, Strauch, Konstantin, Hofman, Albert, Uitterlinden, Andre G., Waldenberger, Melanie, Wichmann, H. Erich, Davies, Gail, Gow, Alan J., Dalbeth, Nicola, Stamp, Lisa, Smit, Johannes H., Kirin, Mirna, Nagaraja, Ramaiah, Nauck, Matthia, Schurmann, Claudia, Budde, Kathrin, Farrington, Susan M., Theodoratou, Evropi, Jula, Antti, Salomaa, Veikko, Sala, Cinzia, Hengstenberg, Christian, Burnier, Michel, Mägi, Reedik, Klopp, Norman, Kloiber, Stefan, Schipf, Sabine, Ripatti, Samuli, Cabras, Stefano, Soranzo, Nicole, Homuth, Georg, Nutile, Teresa, Munroe, Patricia B., Hastie, Nichola, Campbell, Harry, Rudan, Igor, Cabrera, Claudia, Haley, Chri, Franco, Oscar H., Merriman, Tony R., Gudnason, Vilmundur, Pirastu, Mario, Penninx, Brenda W., Snieder, Harold, Metspalu, Andre, Ciullo, Marina, Pramstaller, Peter P., Van Duijn, Cornelia M., Ferrucci, Luigi, Gambaro, Giovanni, Deary, Ian J., Dunlop, Malcolm G., Wilson, James F., Gasparini, Paolo, Gyllensten, Ulf, Spector, Tim D., Wright, Alan F., Hayward, Caroline, Watkins, Hugh, Perola, Marku, Bochud, Murielle, Linda Kao, W. H., Caulfield, Mark, Toniolo, Daniela, Völzke, Henry, Gieger, Christian, Köttgen, Anna, Vitart, Veronique, Life Course Epidemiology (LCE), Institute for Molecular Medicine Finland, Samuli Olli Ripatti / Principal Investigator, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Epidemiology, Public Health, and Internal Medicine
Subjects: Genetics and Molecular Biology (all), Male, Gout, lcsh:Medicine, Biochemistry, Body Mass Index, Risk Factors, GWAS, ATP Binding Cassette Transporter, Subfamily G, Member 2, Settore MED/14 - NEFROLOGIA, Oxidoreductases Acting on Sulfur Group Donors, lcsh:Science, METABOLIC SYNDROME, INSULIN-RESISTANCE, Membrane Glycoproteins, PLASMA N-GLYCANS, Edar Receptor, Medicine (all), Antigens, Nuclear, Neoplasm Proteins, Female, Medical Genetics, Research Article, Genotype, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, BMI, SDG 3 - Good Health and Well-being, Humans, Agricultural and Biological Sciences (all), Biochemistry, Genetics and Molecular Biology (all), Obesity, GENOME-WIDE ASSOCIATION, Medicinsk genetik, ENVIRONMENT, lcsh:R, TRANSPORTER, serum urate levels, genetic associations, Overweight, Uric Acid, ALKALINE-PHOSPHATASE, Genetic Loci, RISK-FACTORS, Linear Models, lcsh:Q, ATP-Binding Cassette Transporters, 3111 Biomedicine, URIC-ACID LEVELS, Genome-Wide Association Study
Abstract: We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, P-inter= 2.6 x 10(-8)). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDAR-ADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10(-8)), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10(-8)), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10(-4)). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.
Published: 2015

11. Pleiotropy among common genetic loci identified for cardiometabolic disorders and C-reactive protein

Author: Ligthart, S, De Vries, PS, Uitterlinden, AG, Hofman, A, Franco, OH, Chasman, DI, Dehghan, A, Dupuis, J, Barbalic, M, Bis, JC, Eiriksdottir, G, Lu, C, Pellikka, N, Wallaschofski, H, Kettunen, J, Henneman, P, Baumert, J, Strachan, DP, Fuchsberger, C, Vitart, V, Wilson, JF, Paré, G, Naitza, S, Rudock, ME, Surakka, I, De Geus, EJC, Alizadeh, BZ, Guralnik, JMD, Shuldiner, A, Tanaka, T, Zee, RYL, Schnabel, RB, Nambi, V, Kavousi, M, Ripatti, S, Nauck, M, Smith, NL, Smith, AV, Sundvall, J, Scheet, P, Liu, Y, Ruokonen, A, Rose, LM, Larson, MG, Hoogeveen, RC, Freimer, NB, Teumer, A, Tracy, RP, Launer, LJ, Buring, JE, Yamamoto, JF, Folsom, AR, Sijbrands, EJG, Pankow, J, Elliott, P, Keaney, JF, Sun, W, Sarin, AP, Fontes, JD, Badola, S, Astor, BC, Pouta, A, Werda, K, Greiser, KH, Kuss, O, Schwabedissen, HEMZ, Thiery, J, Jamshidi, Y, Nolte, IM, Soranzo, N, Spector, TD, Völzke, H, Parker, AN, Aspelund, T, Bates, D, Young, L, Tsui, K, Siscovick, DS, Guo, X, Rotter, JI, Uda, M, Schlessinger, D, Rudan, I, Hicks, AA, Penninx, BW, Thorand, B, Gieger, C, Coresh, J, Willemsen, G, Harris, TB, Järvelin, MR, Rice, K, Radke, D, Salomaa, V, Van Dijk, KW, Boerwinkle, E, Vasan, RS, Ferrucci, L, and Gibson, QD
Abstract: © 2015 Ligthart et al. Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.
Published: 2015

12. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations

Author: Okada, Y, Sim, X, Go, Mj, Wu, Jy, Gu, D, Takeuchi, F, Takahashi, A, Maeda, S, Tsunoda, T, Chen, P, Lim, Sc, Wong, Ty, Liu, J, Young, Tl, Aung, T, Seielstad, M, Teo, Yy, Kim, Yj, Lee, Jy, Han, Bg, Kang, D, Chen, Ch, Tsai, Fj, Chang, Lc, Fann, Sj, Mei, H, Rao, Dc, Hixson, Je, Chen, S, Katsuya, T, Isono, M, Ogihara, T, Chambers, Jc, Zhang, W, Kooner, Js, Kidneygen, Consortium, Ckdgen, Consortium, Albrecht, E, Gugc, Consortium, Yamamoto, K, Kubo, M, Nakamura, Y, Kamatani, N, Kato, N, He, J, Chen, Yt, Cho, Ys, Tai, Es, Tanaka, T., Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, Js, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Smith, Gd, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Ferrucci, L, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, van der Heide JJ, Hepkema, Bg, Hernandez Fuentes, M, Hypponen, E, Johnson, T, de Jong PE, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Melander, O, Munroe, Pb, Nordfors, L, Parsa, A, Peltonen, L, Penninx, Bw, Perucha, E, Pouta, A, Prokopenko, I, Roderick, Pj, Ruokonen, A, Samani, Nj, Sanna, S, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Shuldiner, Ar, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Tanaka, T, Ubink Veltmaat LJ, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Mooser, V, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliott, P, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Glazer, Nl, Gao, X, Yang, Q, Smith, Av, O'Connell, Jr, Li, M, Schmidt, H, Isaacs, A, Ketkar, S, Hwang, Sj, Johnson, Ad, Dehghan, A, Teumer, A, Paré, G, Atkinson, Ej, Zeller, T, Lohman, K, Cornelis, Mc, Probst Hensch NM, Kronenberg, F, Tönjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, Lj, Harris, Tb, Rampersaud, E, Mitchell, Bd, Arking, De, Boerwinkle, E, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer IH, Haritunians, T, Lumley, T, Siscovick, D, Psaty, Bm, Zillikens, Mc, Oostra, Ba, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schillert, A, Ziegler, A, Wild, Ps, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, Ts, Illig, T, Klopp, N, Meisinger, C, Wichmann, He, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, Å, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Schreiber, S, Aulchenko, Ys, Felix, Jf, Rivadeneira, F, Uitterlinden, Ag, Hofman, A, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Blankenberg, S, Liu, Y, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Wang, W, Gudnason, V, Coresh, J, Schmidt, R, Shlipak, Mg, van Duijn CM, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Witteman, Jc, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, Cs, Krumsiek, J, Hundertmark, C, Pistis, G, Ruggiero, D, O'Seaghdha, M, Haller, T, Kutalik, Z, Shi, J, Middelberg, Ps, Gaffo, Al, Pirastu, N, Li, G, Huffman, J, Yengo, L, Zhao, Jh, Demirkan, A, Feitosa, Mf, Liu, X, Malerba, Giovanni, Lopez, Lm, Li, X, Kleber, Me, Hicks, Aa, Nolte, Im, Johansson, A, Murgia, F, Peden, Jf, Steri, M, Tenesa, A, Salo, P, Mangino, M, Rose, Lm, Lehtimäki, T, Woodward, Om, Tin, A, Müller, C, Oldmeadow, C, Putku, M, Czamara, D, Kraft, P, Frogheri, L, Thun, Ga, Grotevendt, A, Gislason, Gk, Mcardle, P, Schallert, M, Martin, Ng, Montgomery, Gw, Jacobs DR Jr, Liu, K, D'Adamo, P, Ulivi, S, Rotter, Ji, Navaro, P, Balkau, B, Froguel, P, Esko, T, Salumets, A, Khaw, Kt, Langenberg, C, Kraja, A, Zhang, Q, Scott, Rj, Holliday, Eg, Org, E, Viigimaa, M, Bandinelli, S, Metter, Je, Lupo, Antonio, Trabetti, Elisabetta, Sorice, R, Döring, A, Lattka, E, Strauch, K, Theis, F, Waldenberger, M, Davies, G, Gow, Aj, Bruinenberg, M, Stolk, Rp, Winkelmann, Br, Boehm, Bo, Lucae, S, Curhan, G, Mudgal, P, Plenge, Rm, Portas, L, Persico, I, Kirin, M, Mateo Leach, I, van Gilst WH, Goel, A, Ongen, H, von Eckardstein, A, Cucca, F, Nagaraja, R, Piras, Mg, Schurmann, C, Budde, K, Ernst, F, Farrington, Sm, Theodoratou, E, Jula, A, Perola, M, Salomaa, V, Shin, Sy, Sala, C, Kähönen, M, Viikari, J, Hengstenberg, C, Nelson, Cp, Meschia, Jf, Nalls, Ma, Sharma, P, Singleton, Ab, Burnier, M, Attia, J, Laan, M, Hillege, Hl, Kloiber, S, Choi, H, Pirastu, M, Tore, S, Whitfield, Jb, Fornage, M, Gasparini, P, Siscovick, Ds, Bouatia Naji, N, Metspalu, A, Borecki, Ib, Gambaro, G, Deary, Ij, Wolffenbuttel, Bh, März, W, Watkins, H, Schipf, S, Dunlop, Mg, Ripatti, S, Toniolo, D, Raitakari, O, Ciullo, M, Caulfield, M, Gieger, C., Okada, Y, Sim, X, Go, Mj, Wu, Jy, Gu, D, Takeuchi, F, Takahashi, A, Maeda, S, Tsunoda, T, Chen, P, Lim, Sc, Wong, Ty, Liu, J, Young, Tl, Aung, T, Seielstad, M, Teo, Yy, Kim, Yj, Lee, Jy, Han, Bg, Kang, D, Chen, Ch, Tsai, Fj, Chang, Lc, Fann, Sj, Mei, H, Rao, Dc, Hixson, Je, Chen, S, Katsuya, T, Isono, M, Ogihara, T, Chambers, Jc, Zhang, W, Kooner, J, Albrecht, E, Yamamoto, K, Kubo, M, Nakamura, Y, Kamatani, N, Kato, N, He, J, Chen, Yt, Cho, Y, Tai, E, Tanaka, T, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Smith, Gd, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Ferrucci, L, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, van der Heide, Jj, Hepkema, Bg, Hernandez Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Melander, O, Munroe, Pb, Nordfors, L, Parsa, A, Peltonen, L, Penninx, Bw, Perucha, E, Pouta, A, Prokopenko, I, Roderick, Pj, Ruokonen, A, Samani, Nj, Sanna, S, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Shuldiner, Ar, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink Veltmaat, Lj, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Mooser, V, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliott, P, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Glazer, Nl, Gao, X, Yang, Q, Smith, Av, O'Connell, Jr, Li, M, Schmidt, H, Isaacs, A, Ketkar, S, Hwang, Sj, Johnson, Ad, Dehghan, A, Teumer, A, Paré, G, Atkinson, Ej, Zeller, T, Lohman, K, Cornelis, Mc, Probst Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, Lj, Harris, Tb, Rampersaud, E, Mitchell, Bd, Arking, De, Boerwinkle, E, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer, Ih, Haritunians, T, Lumley, T, Siscovick, D, Psaty, Bm, Zillikens, Mc, Oostra, Ba, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schillert, A, Ziegler, A, Wild, P, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Illig, T, Klopp, N, Meisinger, C, Wichmann, He, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, Å, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Schreiber, S, Aulchenko, Y, Felix, Jf, Rivadeneira, F, Uitterlinden, Ag, Hofman, A, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Blankenberg, S, Liu, Y, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Wang, W, Gudnason, V, Coresh, J, Schmidt, R, Shlipak, Mg, van Duijn, Cm, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Witteman, Jc, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Krumsiek, J, Hundertmark, C, Pistis, G, Ruggiero, D, O'Seaghdha, M, Haller, T, Kutalik, Z, Shi, J, Middelberg, P, Gaffo, Al, Pirastu, Nicola, Li, G, Huffman, J, Yengo, L, Zhao, Jh, Demirkan, A, Feitosa, Mf, Liu, X, Malerba, G, Lopez, Lm, Li, X, Kleber, Me, Hicks, Aa, Nolte, Im, Johansson, A, Murgia, F, Peden, Jf, Steri, M, Tenesa, A, Salo, P, Mangino, M, Rose, Lm, Lehtimäki, T, Woodward, Om, Tin, A, Müller, C, Oldmeadow, C, Putku, M, Czamara, D, Kraft, P, Frogheri, L, Thun, Ga, Grotevendt, A, Gislason, Gk, Mcardle, P, Schallert, M, Martin, Ng, Montgomery, Gw, Jacobs DR, Jr, Liu, K, D'Adamo, ADAMO PIO, Ulivi, S, Rotter, Ji, Navaro, P, Balkau, B, Froguel, P, Esko, T, Salumets, A, Khaw, Kt, Langenberg, C, Kraja, A, Zhang, Q, Scott, Rj, Holliday, Eg, Org, E, Viigimaa, M, Bandinelli, S, Metter, Je, Lupo, A, Trabetti, E, Sorice, R, Döring, A, Lattka, E, Strauch, K, Theis, F, Waldenberger, M, Davies, G, Gow, Aj, Bruinenberg, M, Stolk, Rp, Winkelmann, Br, Boehm, Bo, Lucae, S, Curhan, G, Mudgal, P, Plenge, Rm, Portas, L, Persico, I, Kirin, M, Mateo Leach, I, van Gilst, Wh, Goel, A, Ongen, H, von Eckardstein, A, Cucca, F, Nagaraja, R, Piras, Mg, Schurmann, C, Budde, K, Ernst, F, Farrington, Sm, Theodoratou, E, Jula, A, Perola, M, Salomaa, V, Shin, Sy, Sala, C, Kähönen, M, Viikari, J, Hengstenberg, C, Nelson, Cp, Meschia, Jf, Nalls, Ma, Sharma, P, Singleton, Ab, Burnier, M, Attia, J, Laan, M, Hillege, Hl, Kloiber, S, Choi, H, Pirastu, M, Tore, S, Whitfield, Jb, Fornage, M, Gasparini, Paolo, Bouatia Naji, N, Metspalu, A, Borecki, Ib, Gambaro, G, Deary, Ij, Wolffenbuttel, Bh, März, W, Watkins, H, Schipf, S, Dunlop, Mg, Ripatti, S, Toniolo, D, Raitakari, O, Ciullo, M, Caulfield, M, Gieger, C., KidneyGen Consortium, CKDGen Consortium, GUGC consortium, Chambers, J.C., Zhang, W., Lord, G.M., van der Harst, P., Lawlor, D.A., Sehmi, J.S., Gale, D.P., Wass, M.N., Ahmadi, K.R., Bakker, S.J., Beckmann, J., Bilo, H.J., Bochud, M., Brown, M.J., Caulfield, M.J., Connell, J.M., Cook, H.T., Cotlarciuc, I., Smith, G.D., de Silva, R., Deng, G., Devuyst, O., Dikkeschei, L.D., Dimkovic, N., Dockrell, M., Dominiczak, A., Ebrahim, S., Eggermann, T., Farrall, M., Ferrucci, L., Floege, J., Forouhi, N.G., Gansevoort, R.T., Han, X., Hedblad, B., van der Heide, J.J., Hepkema, B.G., Hernandez-Fuentes, M., Hypponen, E., Johnson, T., de Jong, P.E., Kleefstra, N., Lagou, V., Lapsley, M., Li, Y., Loos, R.J., Luan, J., Luttropp, K., Maréchal, C., Melander, O., Munroe, P.B., Nordfors, L., Parsa, A., Peltonen, L., Penninx, B.W., Perucha, E., Pouta, A., Prokopenko, I., Roderick, P.J., Ruokonen, A., Samani, N.J., Sanna, S., Schalling, M., Schlessinger, D., Schlieper, G., Seelen, M.A., Shuldiner, A.R., Sjögren, M., Smit, J.H., Snieder, H., Soranzo, N., Spector, T.D., Stenvinkel, P., Sternberg, M.J., Swaminathan, R., Tanaka, T., Ubink-Veltmaat, L.J., Uda, M., Vollenweider, P., Wallace, C., Waterworth, D., Zerres, K., Waeber, G., Wareham, N.J., Maxwell, P.H., McCarthy, M.I., Jarvelin, M.R., Mooser, V., Abecasis, G.R., Lightstone, L., Scott, J., Navis, G., Elliott, P., Kooner, J.S., Köttgen, A., Pattaro, C., Böger, C.A., Fuchsberger, C., Olden, M., Glazer, N.L., Gao, X., Yang, Q., Smith, A.V., O'Connell, J.R., Li, M., Schmidt, H., Isaacs, A., Ketkar, S., Hwang, S.J., Johnson, A.D., Dehghan, A., Teumer, A., Paré, G., Atkinson, E.J., Zeller, T., Lohman, K., Cornelis, M.C., Probst-Hensch, N.M., Kronenberg, F., Tönjes, A., Hayward, C., Aspelund, T., Eiriksdottir, G., Launer, L.J., Harris, T.B., Rampersaud, E., Mitchell, B.D., Arking, D.E., Boerwinkle, E., Struchalin, M., Cavalieri, M., Singleton, A., Giallauria, F., Metter, J., de Boer, I.H., Haritunians, T., Lumley, T., Siscovick, D., Psaty, B.M., Zillikens, M.C., Oostra, B.A., Feitosa, M., Province, M., de Andrade, M., Turner, S.T., Schillert, A., Ziegler, A., Wild, P.S., Schnabel, R.B., Wilde, S., Munzel, T.F., Leak, T.S., Illig, T., Klopp, N., Meisinger, C., Wichmann, H.E., Koenig, W., Zgaga, L., Zemunik, T., Kolcic, I., Minelli, C., Hu, F.B., Johansson, Å., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Schreiber, S., Aulchenko, Y.S., Felix, J.F., Rivadeneira, F., Uitterlinden, A.G., Hofman, A., Imboden, M., Nitsch, D., Brandstätter, A., Kollerits, B., Kedenko, L., Mägi, R., Stumvoll, M., Kovacs, P., Boban, M., Campbell, S., Endlich, K., Völzke, H., Kroemer, H.K., Nauck, M., Völker, U., Polasek, O., Vitart, V., Badola, S., Parker, A.N., Ridker, P.M., Kardia, S.L., Blankenberg, S., Liu, Y., Curhan, G.C., Franke, A., Rochat, T., Paulweber, B., Wang, W., Gudnason, V., Coresh, J., Schmidt, R., Shlipak, M.G., van Duijn, C.M., Borecki, I., Krämer, B.K., Rudan, I., Gyllensten, U., Wilson, J.F., Witteman, J.C., Pramstaller, P.P., Rettig, R., Hastie, N., Chasman, D.I., Kao, W.H., Heid, I.M., Fox, C.S., Albrecht, E., Krumsiek, J., Hundertmark, C., Pistis, G., Ruggiero, D., O'Seaghdha, M., Haller, T., Kutalik, Z., Shi, J., Middelberg, P.S., Gaffo, A.L., Pirastu, N., Li, G., Huffman, J., Yengo, L., Zhao, J.H., Demirkan, A., Feitosa, M.F., Liu, X., Malerba, G., Lopez, L.M., Li, X., Kleber, M.E., Hicks, A.A., Nolte, I.M., Johansson, A., Murgia, F., Peden, J.F., Steri, M., Tenesa, A., Salo, P., Mangino, M., Rose, L.M., Lehtimäki, T., Woodward, O.M., Okada, Y., Tin, A., Müller, C., Oldmeadow, C., Putku, M., Czamara, D., Kraft, P., Frogheri, L., Thun, G.A., Grotevendt, A., Gislason, G.K., McArdle, P., Schallert, M., Martin, N.G., Montgomery, G.W., Kubo, M., Nakamura, Y., Jacobs, D.R., Liu, K., D'Adamo, P., Ulivi, S., Rotter, J.I., Navaro, P., Balkau, B., Froguel, P., Esko, T., Salumets, A., Khaw, K.T., Langenberg, C., Kraja, A., Zhang, Q., Scott, R.J., Holliday, E.G., Org, E., Viigimaa, M., Bandinelli, S., Metter, J.E., Lupo, A., Trabetti, E., Sorice, R., Döring, A., Lattka, E., Strauch, K., Theis, F., Waldenberger, M., Davies, G., Gow, A.J., Bruinenberg, M., Stolk, R.P., Winkelmann, B.R., Boehm, B.O., Lucae, S., Curhan, G., Mudgal, P., Plenge, R.M., Portas, L., Persico, I., Kirin, M., Mateo Leach, I., van Gilst, W.H., Goel, A., Ongen, H., von Eckardstein, A., Cucca, F., Nagaraja, R., Piras, M.G., Schurmann, C., Budde, K., Ernst, F., Farrington, S.M., Theodoratou, E., Jula, A., Perola, M., Salomaa, V., Shin, S.Y., Sala, C., Kähönen, M., Viikari, J., Hengstenberg, C., Nelson, C.P., Meschia, J.F., Nalls, M.A., Sharma, P., Singleton, A.B., Kamatani, N., Burnier, M., Attia, J., Laan, M., Hillege, H.L., Kloiber, S., Choi, H., Pirastu, M., Tore, S., Whitfield, J.B., Fornage, M., Gasparini, P., Siscovick, D.S., Bouatia-Naji, N., Metspalu, A., Borecki, I.B., Gambaro, G., Deary, I.J., Wolffenbuttel, B.H., März, W., Watkins, H., Schipf, S., Dunlop, M.G., Ripatti, S., Toniolo, D., Raitakari, O., Ciullo, M., Caulfield, M., Obstetrics & Gynecology, Medical Informatics, Okada, Yukinori, Sim, Xueling, Go, Min Jin, Wu, Jer-Yuarn, Gu, Dongfeng, Takeuchi, Fumihiko, Takahashi, Atsushi, Maeda, Shiro, Tsunoda, Tatsuhiko, Chen, Peng, Lim, Su-Chi, Wong, Tien-Yin, Liu, Jianjun, Young, Terri L., Aung, Tin, Seielstad, Mark, Teo, Yik-Ying, Kim, Young Jin, Lee, Jong-Young, Han, Bok-Ghee, Kang, Daehee, Chen, Chien-Hsiun, Tsai, Fuu-Jen, Chang, Li-Ching, Cathy Fann, S. -J. C., Mei, Hao, Rao, Dabeeru C., Hixson, James E., Chen, Shufeng, Katsuya, Tomohiro, Isono, Masato, Ogihara, Toshio, Chambers, John C., Zhang, Weihua, Kooner, Jaspal S., Albrecht, Eva, Yamamoto, Kazuhiko, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Kato, Norihiro, He, Jiang, Chen, Yuan-Tsong, Cho, Yoon Shin, Tai, E-Shyong, Tanaka, Toshihiro, de Silva, R Deng G, Hernandez-Fuentes, M, Ubink-Veltmaat, Lj, Probst-Hensch, Nm, Giallauria, Francesco, Pirastu, N, D'Adamo, P, Gasparini, P, and Bouatia-Naji, N
Subjects: Asian Continental Ancestry Group, kidney, Population, Renal function, Genome-wide association study, Biology, Kidney, Polymorphism, Single Nucleotide, Article, Blood Urea Nitrogen, Cohort Studies, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, Asian People, loci, Asian, medicine, Humans, genetics, Genetic Predisposition to Disease, Renal Insufficiency, Chronic, education, meta-analysis, Genome-Wide Association Study, Genetic association, Genetics, Creatinine, education.field_of_study, ta3121, medicine.disease, Uric Acid, Asian Continental Ancestry Group/genetics, Creatinine/blood, Glomerular Filtration Rate/genetics, Kidney/physiology, Renal Insufficiency, Chronic/genetics, Uric Acid/blood, medicine.anatomical_structure, chemistry, Genetic epidemiology, Cohort Studie, Human, Kidney disease, Glomerular Filtration Rate
Abstract: Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genomewide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 x 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of similar to 110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.
Published: 2012

13. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author: Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, Fox, CS, Pattaro, C, Teumer, A, Gorski, M, Chu, AY, Li, M, Mijatovic, V, Garnaas, M, Tin, A, Sorice, R, Li, Y, Taliun, D, Olden, M, Foster, M, Yang, Q, Chen, M-H, Pers, TH, Johnson, AD, Ko, Y-A, Fuchsberger, C, Tayo, B, Nalls, M, Feitosa, MF, Isaacs, A, Dehghan, A, d'Adamo, P, Adeyemo, A, Dieffenbach, AK, Zonderman, AB, Nolte, IM, van der Most, PJ, Wright, AF, Shuldiner, AR, Morrison, AC, Hofman, A, Smith, AV, Dreisbach, AW, Franke, A, Uitterlinden, AG, Metspalu, A, Tonjes, A, Lupo, A, Robino, A, Johansson, A, Demirkan, A, Kollerits, B, Freedman, BI, Ponte, B, Oostra, BA, Paulweber, B, Kraemer, BK, Mitchell, BD, Buckley, BM, Peralta, CA, Hayward, C, Helmer, C, Rotimi, CN, Shaffer, CM, Mueller, C, Sala, C, van Duijn, CM, Saint-Pierre, A, Ackermann, D, Shriner, D, Ruggiero, D, Toniolo, D, Lu, Y, Cusi, D, Czamara, D, Ellinghaus, D, Siscovick, DS, Ruderfer, D, Gieger, C, Grallert, H, Rochtchina, E, Atkinson, EJ, Holliday, EG, Boerwinkle, E, Salvi, E, Bottinger, EP, Murgia, F, Rivadeneira, F, Ernst, F, Kronenberg, F, Hu, FB, Navis, GJ, Curhan, GC, Ehret, GB, Homuth, G, Coassin, S, Thun, G-A, Pistis, G, Gambaro, G, Malerba, G, Montgomery, GW, Eiriksdottir, G, Jacobs, G, Li, G, Wichmann, H-E, Campbell, H, Schmidt, H, Wallaschofski, H, Voelzke, H, Brenner, H, Kroemer, HK, Kramer, H, Lin, H, Leach, IM, Ford, I, Guessous, I, Rudan, I, Prokopenko, I, Borecki, I, Heid, IM, Kolcic, I, Persico, I, Jukema, JW, Wilson, JF, Felix, JF, Divers, J, Lambert, J-C, Stafford, JM, Gaspoz, J-M, Smith, JA, Faul, JD, Wang, JJ, Ding, J, Hirschhorn, JN, Attia, J, Whitfield, JB, Chalmers, J, Viikari, J, Coresh, J, Denny, JC, Karjalainen, J, Fernandes, JK, Endlich, K, Butterbach, K, Keene, KL, Lohman, K, Portas, L, Launer, LJ, Lyytikaeinen, L-P, Yengo, L, Franke, L, Ferrucci, L, Rose, LM, Kedenko, L, Rao, M, Struchalin, M, Kleber, ME, Cavalieri, M, Haun, M, Cornelis, MC, Ciullo, M, Pirastu, M, de Andrade, M, McEvoy, MA, Woodward, M, Adam, M, Cocca, M, Nauck, M, Imboden, M, Waldenberger, M, Pruijm, M, Metzger, M, Stumvoll, M, Evans, MK, Sale, MM, Kaehoenen, M, Boban, M, Bochud, M, Rheinberger, M, Verweij, N, Bouatia-Naji, N, Martin, NG, Hastie, N, Probst-Hensch, N, Soranzo, N, Devuyst, O, Raitakari, O, Gottesman, O, Franco, OH, Polasek, O, Gasparini, P, Munroe, PB, Ridker, PM, Mitchell, P, Muntner, P, Meisinger, C, Smit, JH, Kovacs, P, Wild, PS, Froguel, P, Rettig, R, Maegi, R, Biffar, R, Schmidt, R, Middelberg, RPS, Carroll, RJ, Penninx, BW, Scott, RJ, Katz, R, Sedaghat, S, Wild, SH, Kardia, SLR, Ulivi, S, Hwang, S-J, Enroth, S, Kloiber, S, Trompet, S, Stengel, B, Hancock, SJ, Turner, ST, Rosas, SE, Stracke, S, Harris, TB, Zeller, T, Zemunik, T, Lehtimaeki, T, Illig, T, Aspelund, T, Nikopensius, T, Esko, T, Tanaka, T, Gyllensten, U, Voelker, U, Emilsson, V, Vitart, V, Aalto, V, Gudnason, V, Chouraki, V, Chen, W-M, Igl, W, Maerz, W, Koenig, W, Lieb, W, Loos, RJF, Liu, Y, Snieder, H, Pramstaller, PP, Parsa, A, O'Connell, JR, Susztak, K, Hamet, P, Tremblay, J, de Boer, IH, Boeger, CA, Goessling, W, Chasman, DI, Koettgen, A, Kao, WHL, and Fox, CS
Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
Published: 2016

14. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Author: Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, SM, Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K (Kirsten), Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, Loos, RJF, Ried, JS, Jeff, JM, Chu, AY, Bragg-Gresham, JL, Dongen, J, Huffman, JE, Ahluwalia, TS, Cadby, G, Eklund, N, Eriksson, J, Esko, T, Feitosa, MF, Goel, A, Gorski, M, Hayward, C, Heard-Costa, NL, Jackson, AU, Jokinen, E, Kanoni, S, Kristiansson, K, Kutalik, Z, Lahti, J, Luan, JA, Magi, R, Mahajan, A, Mangino, M, Medina-Gomez, C, Monda, KL, Nolte, IM (Ilja), Perusse, L, Prokopenko, I, Qi, L, Rose, LM, Salvi, E, Smith, M T, Snieder, H, Stancakova, A, Sung, YJ, Tachmazidou, I, Teumer, A, Thorleifsson, G, van der Harst, P, Walker, RW, Wang, SR, Wild, SH, Willems, SM, Wong, A, Zhang, WH, Albrecht, E, Alves, AC, Bakker, SJL, Barlassina, C, Bartz, TM, Beilby, J, Bellis, C, Bergman, RN, Bergmann, S, Blangero, J, Bluher, M, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Bruinenberg, M, Campbell, H, Chen, YDI, Chiang, CWK, Chines, PS, Collins, FS, Cucca, F, Cupples, LA, D'Avila, F, de Geus, EJC, Dedoussis, G, Dimitriou, M, Doring, A, Eriksson, JG, Farmaki, AE, Farrall, M, Ferreira, T, Fischer, K (Kirsten), Forouhi, NG, Friedrich, N, Gjesing, AP, Glorioso, N, Graff, M, Grallert, H, Grarup, N, Grassler, J, Grewal, J, Hamsten, A, Harder, MN, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Havulinna, AS, Heliovaara, M, Hillege, H, Hofman, Bert, Holmen, O, Homuth, G, Hottenga, JJ (Jouke Jan), Hui, JN, Husemoen, LL, Hysi, PG, Isaacs, Aaron, Ittermann, T, Jalilzadeh, S, James, AL, Jorgensen, T, Jousilahti, P, Jula, A, Justesen, JM, Justice, AE, Kahonen, M, Karaleftheri, M, Khaw, KT, Keinanen-Kiukaanniemi, SM, Kinnunen, L, Knekt, PB, Koistinen, HA, Kolcic, I, Kooner, IK, Koskinen, S, Kovacs, P, Kyriakou, T, Laitinen, T, Langenberg, C, Lewin, AM, Lichtner, P, Lindgren, CM, Lindstrom, J, Linneberg, A, Lorbeer, R, Lorentzon, M, Luben, R, Lyssenko, V, Mannisto, S, Manunta, P, Leach, IM, McArdle, WL, McKnight, B, Mohlke, KL, Mihailov, E, Milani, L, Mills, R, Montasser, ME, Morris, AP, Muller, G, Musk, AW, Narisu, N, Ong, KK, Oostra, B, Osmond, C, Palotie, A, Pankow, JS, Paternoster, L, Penninx, BW, Pichler, I, Pilia, MG, Polasek, O, Pramstaller, PP, Raitakari, OT, Rankinen, T, Rao, DC, Rayner, NW, Ribel-Madsen, R, Rice, TK, Richards, M, Ridker, PM, Rivadeneira, Fernando, Ryan, KA, Sanna, S, Sarzynski, MA, Scholtens, s, Scott, RA, Sebert, S, Southam, L, Sparso, TH, Steinthorsdottir, V, Stirrups, K, Stolk, RP (Ronald), Strauch, K, Stringham, HM, Swertz, MA, Swift, AJ, Tonjes, A, Tsafantakis, E, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vandenput, L, Vartiainen, E, Venturini, C, Verweij, N (Niek), Viikari, JS, Vitart, V, Vohl, MC, Vonk, JM, Waeber, G, Widen, E, Willemsen, G, Wilsgaard, T, Winkler, TW, Wright, AF, Yerges-Armstrong, LM, Zhao, JH, Zillikens, M.C., Boomsma, DI, Bouchard, C, Chambers, JC, Chasman, DI, Cusi, D, Gansevoort, RT, Gieger, C, Hansen, T, Hicks, AA, Hu, F, Hveem, K, Jarvelin, MR, Kajantie, E, Kooner, JS, Kuh, D, Kuusisto, J, Laakso, M, Lakka, TA, Lehtimaki, T, Metspalu, A, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Palmer, LJ, Pedersen, O, Perola, M, Peters, A, Psaty, BM, Puolijoki, H, Rauramaa, R, Rudan, I, Salomaa, V, Schwarz, PEH, Shudiner, A R, Smit, JH, Sorensen, TIA, Spector, TD, Stefansson, K, Stumvoll, M, Tremblay, A, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Volker, U, Vollenweider, P, Wareham, NJ, Watkins, H, Wilson, JF, Zeggini, E, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Duijn, Cornelia, Fox, C, Groop, LC, Heid, IM, Hunter, DJ, Kaplan, RC, McCarthy, MI, North, KE, O'Connell, JR, Schlessinger, D, Thorsteinsdottir, U, Strachan, DP, Frayling, T, Hirschhorn, JN, Muller-Nurasyid, M, and Loos, RJF
Published: 2016

15. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Author: Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, Kavousi M, Baumeister SE, Hottenga JJ, de Geus EJ, Penninx BW, Willemsen G, AlcGen Consortium, DIAGRAM+ Study, GIANT Consortium, Global Lipids Genetics Consortium, GOLD Consortium, ICBP-GWAS, MAGIC, Abecasis GR, Ahmadi KR, Boomsma DI, Fox CS, Ala-Korpela M, Stefansson K, Vollenweider P, Vxf6lzke H, Schadt EE, Scott J, Jxe4rvelin MR, Elliott P, Kooner JS, Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, Kavousi M, Baumeister SE, Hottenga JJ, de Geus EJ, Penninx BW, Willemsen G, AlcGen Consortium, MAGIC, Abecasis GR, Ahmadi KR, Boomsma DI, Fox CS, Ala-Korpela M, Stefansson K, Vollenweider P, Vxf6lzke H, Schadt EE, Scott J, Jxe4rvelin MR, Elliott P, and Kooner JS
Published: 2011

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

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

17. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Author: Chambers JC, Zhang W, Sehmi J, Li X, Wass MN, Van der Harst P, Holm H, Sanna S, Kavousi M, Baumeister SE, Coin LJ, Deng G, Gieger C, Heard Costa NL, Hottenga JJ, Kühnel B, Kumar V, Lagou V, Liang L, Luan J, Vidal PM, Mateo Leach I, O'Reilly PF, Peden JF, Rahmioglu N, Soininen P, Speliotes EK, Yuan X, Thorleifsson G, Alizadeh BZ, Atwood LD, Borecki IB, Brown MJ, Charoen P, Cucca F, Das D, de Geus EJ, Dixon AL, Döring A, Ehret G, Eyjolfsson GI, Farrall M, Forouhi NG, Friedrich N, Goessling W, Gudbjartsson DF, Harris TB, Hartikainen AL, Heath S, Hirschfield GM, Hofman A, Homuth G, Hyppönen E, Janssen HL, Johnson T, Kangas AJ, Kema IP, Kühn JP, Lai S, Lathrop M, Lerch MM, Li Y, Liang TJ, Lin JP, Loos RJ, Martin NG, Moffatt MF, Montgomery GW, Munroe PB, Musunuru K, Nakamura Y, O'Donnell CJ, Olafsson I, Penninx BW, Pouta A, Prins BP, Prokopenko I, Puls R, Ruokonen A, Savolainen MJ, Schlessinger D, Schouten JN, Seedorf U, Sen Chowdhry S, Siminovitch KA, Smit JH, Spector TD, Tan W, Teslovich TM, Tukiainen T, Uitterlinden AG, Van der Klauw MM, Vasan RS, Wallace C, Wallaschofski H, Wichmann HE, Willemsen G, Würtz P, Xu C, Yerges Armstrong LM, Alcohol Genome wide Association Consortium, Diabetes Genetics Replication, Meta analyses Study, Genetic Investigation of Anthropometric Traits Consortium, Global Lipids Genetics Consortium, Genetics of Liver Disease Consortium, International Consortium for Blood Pressure, Meta analyses of Glucose, Insulin Related Traits Consortium, Abecasis GR, Ahmadi KR, Boomsma DI, Caulfield M, Cookson WO, van Duijn CM, Froguel P, Matsuda K, McCarthy MI, Meisinger C, Mooser V, Pietiläinen KH, Schumann G, Snieder H, Sternberg MJ, Stolk RP, Thomas HC, Thorsteinsdottir U, Uda M, Waeber G, Wareham NJ, Waterworth DM, Watkins H, Whitfield JB, Witteman JC, Wolffenbuttel BH, Fox CS, Ala Korpela M, Stefansson K, Vollenweider P, Völzke H, Schadt EE, Scott J, Järvelin MR, Elliott P, Kooner JS, PAOLISSO, Giuseppe, Chambers, Jc, Zhang, W, Sehmi, J, Li, X, Wass, Mn, Van der Harst, P, Holm, H, Sanna, S, Kavousi, M, Baumeister, Se, Coin, Lj, Deng, G, Gieger, C, Heard Costa, Nl, Hottenga, Jj, Kühnel, B, Kumar, V, Lagou, V, Liang, L, Luan, J, Vidal, Pm, Mateo Leach, I, O'Reilly, Pf, Peden, Jf, Rahmioglu, N, Soininen, P, Speliotes, Ek, Yuan, X, Thorleifsson, G, Alizadeh, Bz, Atwood, Ld, Borecki, Ib, Brown, Mj, Charoen, P, Cucca, F, Das, D, de Geus, Ej, Dixon, Al, Döring, A, Ehret, G, Eyjolfsson, Gi, Farrall, M, Forouhi, Ng, Friedrich, N, Goessling, W, Gudbjartsson, Df, Harris, Tb, Hartikainen, Al, Heath, S, Hirschfield, Gm, Hofman, A, Homuth, G, Hyppönen, E, Janssen, Hl, Johnson, T, Kangas, Aj, Kema, Ip, Kühn, Jp, Lai, S, Lathrop, M, Lerch, Mm, Li, Y, Liang, Tj, Lin, Jp, Loos, Rj, Martin, Ng, Moffatt, Mf, Montgomery, Gw, Munroe, Pb, Musunuru, K, Nakamura, Y, O'Donnell, Cj, Olafsson, I, Penninx, Bw, Pouta, A, Prins, Bp, Prokopenko, I, Puls, R, Ruokonen, A, Savolainen, Mj, Schlessinger, D, Schouten, Jn, Seedorf, U, Sen Chowdhry, S, Siminovitch, Ka, Smit, Jh, Spector, Td, Tan, W, Teslovich, Tm, Tukiainen, T, Uitterlinden, Ag, Van der Klauw, Mm, Vasan, R, Wallace, C, Wallaschofski, H, Wichmann, He, Willemsen, G, Würtz, P, Xu, C, Yerges Armstrong, Lm, Alcohol Genome wide Association, Consortium, Diabetes Genetics, Replication, Meta analyses, Study, Genetic Investigation of Anthropometric Traits, Consortium, Global Lipids Genetics, Consortium, Genetics of Liver Disease, Consortium, International Consortium for Blood, Pressure, Meta analyses of, Glucose, Insulin Related Traits, Consortium, Abecasis, Gr, Ahmadi, Kr, Boomsma, Di, Caulfield, M, Cookson, Wo, van Duijn, Cm, Froguel, P, Matsuda, K, Mccarthy, Mi, Meisinger, C, Mooser, V, Pietiläinen, Kh, Schumann, G, Snieder, H, Sternberg, Mj, Stolk, Rp, Thomas, Hc, Thorsteinsdottir, U, Uda, M, Waeber, G, Wareham, Nj, Waterworth, Dm, Watkins, H, Whitfield, Jb, Witteman, Jc, Wolffenbuttel, Bh, Fox, C, Ala Korpela, M, Stefansson, K, Vollenweider, P, Völzke, H, Schadt, Ee, Scott, J, Järvelin, Mr, Elliott, P, Kooner, J, and Paolisso, Giuseppe
Published: 2011

18. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

Author: Vimaleswaran, KS, Cavadino, A, Berry, DJ, Jorde, R, Dieffenbach, AK, Lu, C, Alves, AC, Heerspink, HJL, Tikkanen, E, Eriksson, J, Wong, A, Mangino, M, Jablonski, KA, Nolte, IM, Houston, DK, Ahluwalia, TS, Van der Most, PJ, Pasko, D, Zgaga, L, Thiering, E, Vitart, V, Fraser, RM, Huffman, JE, De Boer, RA, Schoettker, B, Saum, K-U, McCarthy, MI, Dupuis, J, Herzig, K-H, Sebert, S, Pouta, A, Laitinen, J, Kleber, ME, Navis, G, Lorentzon, M, Jameson, K, Arden, N, Cooper, JA, Acharya, J, Hardy, R, Raitakari, O, Ripatti, S, Billings, LK, Lahti, J, Osmond, C, Penninx, BW, Rejnmark, L, Lohman, KK, Paternoster, L, Stolk, RP, Hernandez, DG, Byberg, L, Hagstrom, E, Melhus, H, Ingelsson, E, Mellstroem, D, Ljunggren, O, Tzoulaki, I, McLachlan, S, Theodoratou, E, Tiesler, CMT, Jula, A, Navarro, P, Wright, AF, Polasek, O, Hayward, C, Wilson, JF, Rudan, I, Salomaa, V, Heinrich, J, Campbell, H, Price, JF, Karlsson, M, Lind, L, Michaesson, K, Bandinelli, S, Frayling, TM, Hartman, CA, Sorensen, TIA, Kritchevsky, SB, Langdahl, BL, Eriksson, JG, Florez, JC, Spector, TD, Lehtimaki, T, Kuh, D, Humphries, SE, Cooper, C, Ohlsson, C, Maerz, W, De Borst, MH, Kumari, M, Kivimaki, M, Wang, TJ, Power, C, Brenner, H, Grimnes, G, Van der Harst, P, Snieder, H, Hingorani, AD, Pilz, S, Whittaker, JC, Jarvelin, M-R, and Hypponen, E
Subjects: Adult, Male, Caroline Hayward, D SUPPLEMENTATION, Oxidoreductases Acting on CH-CH Group Donors, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, Polymorphism, Single Nucleotide, DISEASE, Body Mass Index, 1117 Public Health and Health Services, Endocrinology & Metabolism, KIDNEY, GENETIC-VARIANTS, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Vitamin D, Cytochrome P450 Family 2, LifeLines Cohort Study investigators, Randomized Controlled Trials as Topic, OUTCOMES, Science & Technology, 1103 Clinical Sciences, Mendelian Randomization Analysis, Middle Aged, Vitamin D Deficiency, Phenotype, 1101 Medical Biochemistry and Metabolomics, Hypertension, Cholestanetriol 26-Monooxygenase, Global Blood Pressure Genetics (Global BPGen) consortium, TRIAL, Female, HEALTH, Life Sciences & Biomedicine, International Consortium for Blood Pressure (ICBP)
Abstract: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study. Funding British Heart Foundation, UK Medical Research Council, and Academy of Finland.
Published: 2014

19. Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study

Author: Vimaleswaran, Kerani S., Cavadino, Alana, Berry, Diane J., Jorde, Rolf, Grimnes, Guri, Dieffenbach, Aida Karina, Lu, Chen, Alves, Alexessander Couto, Heerspink, Hiddo J. Lambers, Tikkanen, Emmi, Eriksson, Joel, Wong, Andrew, Mangino, Massimo, Jablonski, Kathleen A., Nolte, Ilja M., Houston, Denise K., Ahluwalia, Tarunveer Singh, van der Most, Peter J., Pasko, Dorota, Zgaga, Lina, Thiering, Elisabeth, Schöttker, B, Saum, KU, Brenner, H, Järvelin, MR, Tzoulaki, I, Snieder, H, Stolk, RP, Hartman, CA, de Boer, RA, van der Harst, P, Navis, G, de Borst, MH, Lorentzon, M, Mellström, D, Ohlsson, C, Hardy, R, Kuh, D, Cooper, JA, Acharya, J, Humphries, SE, Hingorani, AD, Kumari, M, Kivimaki, M, Spector, TD, Kritchevsky, SB, Lohman, KK, Sørensen, TIA, Frayling, TM, Campbell, H, Theodoratou, E, Fraser, RM, Wilson, JF, Rudan, I, Price, JF, McLachlan, S, Vitart, V, Navarro, P, Huffman, JE, Hayward, C, Wright, AF, Tiesler, CMT, Heinrich, J, McCarthy, MI, Ingelsson, E, Arden, N, Cooper, C, Dupuis, J, Herzig, KH, Sebert, S, Pouta, A, Laitinen, J, Kleber, ME, März, W, Jameson, K, Osmond, C, Raitakari, O, Ripatti, S, Lahti, J, Eriksson, JG, Penninx, BW, Billings, LK, Florez, JC, Rejnmark, L, Langdahl, BL, Paternoster, L, Hernandez, DG, Byberg, L, Michaelsson, K, Hagström, E, Melhus, H, Ljunggren, O, Lind, L, Jula, A, Polasek, O, Salomaa, V, Karlsson, M, Bandinelli, S, Lehtimäki, T, Wang, TJ, Pilz, S, and Whittaker, JC
Abstract: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that aff ect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, –0·12 mm Hg, 95% CI –0·20 to –0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, –0·02 mm Hg, –0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of –0·10 mm Hg in systolic blood pressure (–0·21 to –0·0001; p=0·0498) and a change of –0·08 mm Hg in diastolic blood pressure (–0·15 to –0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of –0·29 mm Hg in diastolic blood pressure (–0·52 to –0·07; p=0·01), a change of –0·37 mm Hg in systolic blood pressure (–0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This fi nding warrants further investigation in an independent, similarly powered study.
Published: 2014

20. New genetic loci link adipose and insulin biology to body fat distribution.

Author: ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., 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K.L.
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

21. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, 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Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap
Published: 2015

22. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, 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Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

23. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Author: Fall T, Hxe4gg S, Mxe4gi R, Ploner A, Fischer K, Horikoshi M, Sarin AP, Thorleifsson G, Ladenvall C, Kals M, Kuningas M, Draisma HH, Ried JS, van Zuydam NR, Huikari V, Hottenga JJ, Willemsen G, Penninx BW, Boomsma DI, de Geus EJ, Morris AD, Groop L, Jxe4rvelin MR, Salomaa V, Vartiainen E, Hofman A, Ripatti S, Metspalu A, Thorsteinsdottir U, Stefansson K, Pedersen NL, McCarthy MI, Ingelsson E, Prokopenko I, European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium, European Network for Genetic, and Genomic Epidemiology (ENGAGE) consortium
Published: 2013
Full Text: View/download PDF

24. Loci influencing blood pressure identified using a cardiovascular gene-centric array (vol 22, pg 1663, 2013)

Author: Ganesh, SK, Tragante, V, Guo, W, Guo, YR, Lanktree, MB, Smith, EN, Johnson, T, Castillo, BA, Barnard, J, Baumert, J, Chang, YPC, Elbers, CC, Farrall, M, Fischer, ME, Franceschini, N, Gaunt, TR, Gho, JMIH, Gieger, C, Gong, Y, Isaacs, Aaron, Kleber, ME, Leach, IM, McDonough, CW, Meijs, MFL, Mellander, O, Molony, CM, Nolte, IM (Ilja), Padmanabhan, S, Price, TS, Rajagopalan, R, Shaffer, J, Shah, S, Shen, HQ, Soranzo, N, van der Most, PJ, Van Iperen, EPA, van Setten, J, Vonk, JM, Zhang, Lei, Beitelshees, AL, Berenson, GS, Bhatt, DL, Boer, JMA, Boerwinkle, E, Burkley, B, Burt, A, Chakravarti, A, Chen, W, Cooper-DeHoff, RM, Curtis, SP, Dreisbach, A, Duggan, D, Ehret, GB, Fabsitz, RR, Fornage, M, Fox, E, Furlong, CE, Gansevoort, RT, Hofker, MH, Hovingh, GK, Kirkland, SA, Kottke-Marchant, K, Kutlar, A, Lacroix, AZ, Langaee, TY, Li, YR, Lin, HH, Liu, K, Maiwald, S, Malik, R, Murugesan, G, Newton-Cheh, C, OConnell, JR, Onland-Moret, NC, Ouwehand, WH, Palmas, W, Penninx, BW, Pepine, CJ, Pettinger, M, Polak, JF, Ramachandran, VS, Ranchalis, J, Redline, S, Ridker, PM, Rose, LM, Scharnag, H, Schork, NJ, Shimbo, D, Shuldiner, AR, Srinivasan, SR (Sathanur), Stolk, RP (Ronald), Taylor, HA, Thorand, B, Trip, MD, Duijn, Cornelia, Verschuren, WM, Wijmenga, C, Winkelmann, BR, Wyatt, S, Young, JH, Boehm, BO, Caulfield, MJ, Chasman, DI, Davidson, KW, Doevendans, PA, FitzGerald, GA, Gums, JG, Hakonarson, H, Hillege, HL, Illig, T, Jarvik, GP, Johnson, JA, Kastelein, JJP, Koenig, W, Marz, W, Mitchell, BD, Murray, SS, Oldehinkel, AJ (A.), Rader, DJ, Reilly, MP, Reiner, AP, Schadt, EE, Silverstein, RL, Snieder, H, Stanton, AV, Uitterlinden, André, van der Harst, P, van der Schouw, YT, Samani, NJ, Johnson, AD, Munroe, PB, de Bakker, PIW, Zhu, XF, Levy, D, Keating, BJ, Asselbergs, FW, Epidemiology, Public Health, Clinical Genetics, Immunology, Child and Adolescent Psychiatry / Psychology, and Internal Medicine
Published: 2013

25. Seventy-five genetic loci influencing the human red blood cell

Author: van der Harst P, Zhang W, Mateo Leach I, Rendon A, Verweij N, Sehmi J, Paul DS, Elling U, Allayee H, Li X, Radhakrishnan A, Tan ST, Voss K, Weichenberger CX, Albers CA, Hottenga JJ, Abdellaoui A, de Geus EJ, de Moor MH, Penninx BW, Willemsen G, Wolffenbuttel BH, Boomsma DI, Beckmann JS, Dedoussis GV, Deloukas P, Ferreira MA, Sanna S, Uda M, Hicks AA, Penninger JM, Gieger C, Kooner JS, Ouwehand WH, Soranzo N, and Chambers JC
Published: 2012

26. Genome-wide meta-analysis of common variant differences between men and women

Author: Boraska V, Jerončić A, Colonna V, Southam L, Nyholt DR, Rayner NW, Perry JR, Toniolo D, Albrecht E, Ang W, Bandinelli S, Barbalic M, Barroso I, Beckmann JS, Biffar R, Boomsma D, Hottenga JJ, Vink JM, Willemsen G, de Geus E, Penninx BW, Schreiber S, Schunkert H, Spector TD, Stumvoll M, Uitterlinden AG, Ulivi S, van der Harst P, Vollenweider P, Vxf6lzke H, Wareham NJ, Wichmann HE, Wilson JF, Rudan I, Xue Y, and Zeggini E
Published: 2012

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

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

28. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author: Wain, LV, Verwoert, GC, O'Reilly, PF, Shi, G, Johnson, T, Johnson, AD, Bochud, M, Rice, KM, Henneman, P, Smith, AV, Ehret, GB, Amin, N, Larson, MG, Mooser, V, Hadley, D, Dörr, M, Bis, JC, Aspelund, T, Esko, T, Janssens, AC, Zhao, JH, Heath, S, Laan, M, Fu, J, Pistis, G, Luan, J, Arora, P, Lucas, G, Pirastu, N, Pichler, I, Jackson, AU, Webster, RJ, Zhang, F, Peden, JF, Schmidt, H, Tanaka, T, Campbell, H, Igl, W, Milaneschi, Y, Hottenga, JJ, Vitart, V, Chasman, DI, Trompet, S, Bragg-Gresham, JL, Alizadeh, BZ, Chambers, JC, Guo, X, Lehtimäki, T, Kühnel, B, Lopez, LM, Polašek, O, Boban, M, Nelson, CP, Morrison, AC, Pihur, V, Ganesh, SK, Hofman, A, Kundu, S, Mattace-Raso, FU, Rivadeneira, F, Sijbrands, EJ, Uitterlinden, AG, Hwang, SJ, Vasan, RS, Wang, TJ, Bergmann, S, Vollenweider, P, Waeber, G, Laitinen, J, Pouta, A, Zitting, P, McArdle, WL, Kroemer, HK, Völker, U, Völzke, H, Glazer, NL, Taylor, KD, Harris, TB, Alavere, H, Haller, T, Keis, A, Tammesoo, ML, Aulchenko, Y, Barroso, I, Khaw, KT, Galan, P, Hercberg, S, Lathrop, M, Eyheramendy, S, Org, E, Sõber, S, Lu, X, Nolte, IM, Penninx, BW, Corre, T, Masciullo, C, Sala, C, Groop, L, Voight, BF, Melander, O, O'Donnell, CJ, Salomaa, V, d'Adamo, AP, Fabretto, A, Faletra, F, Ulivi, S, Del Greco, F, Facheris, M, Collins, FS, Bergman, RN, Beilby, JP, Hung, J, Musk, AW, Mangino, M, Shin, SY, Soranzo, N, Watkins, H, Goel, A, Hamsten, A, Gider, P, Loitfelder, M, Zeginigg, M, Hernandez, D, Najjar, SS, Navarro, P, Wild, SH, Corsi, AM, Singleton, A, de Geus, EJ, Willemsen, G, Parker, AN, Rose, LM, Buckley, B, Stott, D, Orru, M, Uda, M, LifeLines Cohort Study, van der Klauw, MM, Zhang, W, Li, X, Scott, J, Chen, YD, Burke, GL, Kähönen, M, Viikari, J, Döring, A, Meitinger, T, Davies, G, Starr, JM, Emilsson, V, Plump, A, Lindeman, JH, Hoen, PA, König, IR, EchoGen consortium, Felix, JF, Clarke, R, Hopewell, JC, Ongen, H, Breteler, M, Debette, S, Destefano, AL, Fornage, M, AortaGen Consortium, Mitchell, GF, CHARGE Consortium Heart Failure Working Group, Smith, NL, KidneyGen consortium, Holm, H, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, CKDGen consortium, Cardiogenics consortium, CardioGram, Samani, NJ, Preuss, M, Rudan, I, Hayward, C, Deary, IJ, Wichmann, HE, Raitakari, OT, Palmas, W, Kooner, JS, Stolk, RP, Jukema, JW, Wright, AF, Boomsma, DI, Bandinelli, S, Gyllensten, UB, Wilson, JF, Ferrucci, L, Schmidt, R, Farrall, M, Spector, TD, Palmer, LJ, Tuomilehto, J, Pfeufer, A, Gasparini, P, Siscovick, D, Altshuler, D, Loos, RJ, Toniolo, D, Snieder, H, Gieger, C, Meneton, P, Wareham, NJ, Oostra, BA, Metspalu, A, Launer, L, Rettig, R, Strachan, DP, Beckmann, JS, Witteman, JC, Erdmann, J, van Dijk, KW, Boerwinkle, E, Boehnke, M, Ridker, PM, Jarvelin, MR, Chakravarti, A, Abecasis, GR, Gudnason, V, Newton-Cheh, C, Levy, D, Munroe, PB, Psaty, BM, Caulfield, MJ, Rao, DC, Tobin, MD, Elliott, P, and van Duijn, CM
Published: 2011

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

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

30. Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension

Author: Padmanabhan, S, Melander, O, Johnson, T, Di Blasio, AM, Lee, WK, Gentilini, D, Hastie, CE, Menni, C, Monti, MC, Delles, C, Laing, S, Corso, B, Navis, G, Kwakernaak, AJ, van der Harst, P, Bochud, M, Maillard, M, Burnier, M, Hedner, T, Kjeldsen, S, Wahlstrand, B, Sjögren, M, Fava, C, Montagnana, M, Danese, E, Torffvit, O, Hedblad, B, Snieder, H, Connell, JM, Brown, M, Samani, NJ, Farrall, M, Cesana, G, Mancia, G, Signorini, S, Grassi, G, Eyheramendy, S, Wichmann, HE, Laan, M, Strachan, DP, Sever, P, Shields, DC, Stanton, A, Vollenweider, P, Teumer, A, Völzke, H, Rettig, R, Newton-Cheh, C, Arora, P, Zhang, F, Soranzo, N, Spector, TD, Lucas, G, Kathiresan, S, Siscovick, DS, Luan, J, Loos, RJ, Wareham, NJ, Penninx, BW, Nolte, IM, McBride, M, Miller, WH, Nicklin, SA, Baker, AH, Graham, D, McDonald, RA, Pell, JP, Sattar, N, Welsh, P, Global BPgen Consortium, Munroe, P, Caulfield, MJ, Zanchetti, A, and Dominiczak, AF
Abstract: Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5' region of Uromodulin (UMOD; rs13333226, combined P value of 3.6 × 10⁻¹¹). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
Published: 2010

31. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author: Thompson, PM, Stein, JL, Medland, SE, Hibar, DP, Vasquez, AA, Renteria, ME, Toro, R, Jahanshad, N, Schumann, G, Franke, B, Wright, MJ, Martin, NG, Agartz, I, Alda, M, Alhusaini, S, Almasy, L, Almeida, J, Alpert, K, Andreasen, NC, Andreassen, OA, Apostolova, LG, Appel, K, Armstrong, NJ, Aribisala, B, Bastin, ME, Bauer, M, Bearden, CE, Bergmann, O, Binder, EB, Blangero, J, Bockholt, HJ, Boen, E, Bois, C, Boomsma, DI, Booth, T, Bowman, IJ, Bralten, J, Brouwer, RM, Brunner, HG, Brohawn, DG, Buckner, RL, Buitelaar, J, Bulayeva, K, Bustillo, JR, Calhoun, VD, Cannon, DM, Cantor, RM, Carless, MA, Caseras, X, Cavalleri, GL, Chakravarty, MM, Chang, KD, Ching, CRK, Christoforou, A, Cichon, S, Clark, VP, Conrod, P, Coppola, G, Crespo-Facorro, B, Curran, JE, Czisch, M, Deary, IJ, de Geus, EJC, den Braber, A, Delvecchio, G, Depondt, C, de Haan, L, de Zubicaray, GI, Dima, D, Dimitrova, R, Djurovic, S, Dong, H, Donohoe, G, Duggirala, R, Dyer, TD, Ehrlich, S, Ekman, CJ, Elvsashagen, T, Emsell, L, Erk, S, Espeseth, T, Fagerness, J, Fears, S, Fedko, I, Fernandez, G, Fisher, SE, Foroud, T, Fox, PT, Francks, C, Frangou, S, Frey, EM, Frodl, T, Frouin, V, Garavan, H, Giddaluru, S, Glahn, DC, Godlewska, B, Goldstein, RZ, Gollub, RL, Grabe, HJ, Grimm, O, Gruber, O, Guadalupe, T, Gur, RE, Gur, RC, Goering, HHH, Hagenaars, S, Hajek, T, Hall, GB, Hall, J, Hardy, J, Hartman, CA, Hass, J, Hatton, SN, Haukvik, UK, Hegenscheid, K, Heinz, A, Hickie, IB, Ho, B-C, Hoehn, D, Hoekstra, PJ, Hollinshead, M, Holmes, AJ, Homuth, G, Hoogman, M, Hong, LE, Hosten, N, Hottenga, J-J, Pol, HEH, Hwang, KS, Jack, CR, Jenkinson, M, Johnston, C, Joensson, EG, Kahn, RS, Kasperaviciute, D, Kelly, S, Kim, S, Kochunov, P, Koenders, L, Kraemer, B, Kwok, JBJ, Lagopoulos, J, Laje, G, Landen, M, Landman, BA, Lauriello, J, Lawrie, SM, Lee, PH, Le Hellard, S, Lemaitre, H, Leonardo, CD, Li, C-S, Liberg, B, Liewald, DC, Liu, X, Lopez, LM, Loth, E, Lourdusamy, A, Luciano, M, Macciardi, F, Machielsen, MWJ, MacQueen, GM, Malt, UF, Mandl, R, Manoach, DS, Martinot, J-L, Matarin, M, Mather, KA, Mattheisen, M, Mattingsdal, M, Meyer-Lindenberg, A, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Meisenzahl, E, Melle, I, Milaneschi, Y, Mohnke, S, Montgomery, GW, Morris, DW, Moses, EK, Mueller, BA, Munoz Maniega, S, Muehleisen, TW, Mueller-Myhsok, B, Mwangi, B, Nauck, M, Nho, K, Nichols, TE, Nilsson, L-G, Nugent, AC, Nyberg, L, Olvera, RL, Oosterlaan, J, Ophoff, RA, Pandolfo, M, Papalampropoulou-Tsiridou, M, Papmeyer, M, Paus, T, Pausova, Z, Pearlson, GD, Penninx, BW, Peterson, CP, Pfennig, A, Phillips, M, Pike, GB, Poline, J-B, Potkin, SG, Puetz, B, Ramasamy, A, Rasmussen, J, Rietschel, M, Rijpkema, M, Risacher, SL, Roffman, JL, Roiz-Santianez, R, Romanczuk-Seiferth, N, Rose, EJ, Royle, NA, Rujescu, D, Ryten, M, Sachdev, PS, Salami, A, Satterthwaite, TD, Savitz, J, Saykin, AJ, Scanlon, C, Schmaal, L, Schnack, HG, Schork, AJ, Schulz, SC, Schuer, R, Seidman, L, Shen, L, Shoemaker, JM, Simmons, A, Sisodiya, SM, Smith, C, Smoller, JW, Soares, JC, Sponheim, SR, Sprooten, E, Starr, JM, Steen, VM, Strakowski, S, Strike, L, Sussmann, J, Saemann, PG, Teumer, A, Toga, AW, Tordesillas-Gutierrez, D, Trabzuni, D, Trost, S, Turner, J, Van den Heuvel, M, van der Wee, NJ, van Eijk, K, van Erp, TGM, van Haren, NEM, van 't Ent, D, van Tol, M-J, Hernandez, MCV, Veltman, DJ, Versace, A, Voelzke, H, Walker, R, Walter, H, Wang, L, Wardlaw, JM, Weale, ME, Weiner, MW, Wen, W, Westlye, LT, Whalley, HC, Whelan, CD, White, T, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Zilles, D, Zwiers, MP, Thalamuthu, A, Schofield, PR, Freimer, NB, Lawrence, NS, Drevets, W, Thompson, PM, Stein, JL, Medland, SE, Hibar, DP, Vasquez, AA, Renteria, ME, Toro, R, Jahanshad, N, Schumann, G, Franke, B, Wright, MJ, Martin, NG, Agartz, I, Alda, M, Alhusaini, S, Almasy, L, Almeida, J, Alpert, K, Andreasen, NC, Andreassen, OA, Apostolova, LG, Appel, K, Armstrong, NJ, Aribisala, B, Bastin, ME, Bauer, M, Bearden, CE, Bergmann, O, Binder, EB, Blangero, J, Bockholt, HJ, Boen, E, Bois, C, Boomsma, DI, Booth, T, Bowman, IJ, Bralten, J, Brouwer, RM, Brunner, HG, Brohawn, DG, Buckner, RL, Buitelaar, J, Bulayeva, K, Bustillo, JR, Calhoun, VD, Cannon, DM, Cantor, RM, Carless, MA, Caseras, X, Cavalleri, GL, Chakravarty, MM, Chang, KD, Ching, CRK, Christoforou, A, Cichon, S, Clark, VP, Conrod, P, Coppola, G, Crespo-Facorro, B, Curran, JE, Czisch, M, Deary, IJ, de Geus, EJC, den Braber, A, Delvecchio, G, Depondt, C, de Haan, L, de Zubicaray, GI, Dima, D, Dimitrova, R, Djurovic, S, Dong, H, Donohoe, G, Duggirala, R, Dyer, TD, Ehrlich, S, Ekman, CJ, Elvsashagen, T, Emsell, L, Erk, S, Espeseth, T, Fagerness, J, Fears, S, Fedko, I, Fernandez, G, Fisher, SE, Foroud, T, Fox, PT, Francks, C, Frangou, S, Frey, EM, Frodl, T, Frouin, V, Garavan, H, Giddaluru, S, Glahn, DC, Godlewska, B, Goldstein, RZ, Gollub, RL, Grabe, HJ, Grimm, O, Gruber, O, Guadalupe, T, Gur, RE, Gur, RC, Goering, HHH, Hagenaars, S, Hajek, T, Hall, GB, Hall, J, Hardy, J, Hartman, CA, Hass, J, Hatton, SN, Haukvik, UK, Hegenscheid, K, Heinz, A, Hickie, IB, Ho, B-C, Hoehn, D, Hoekstra, PJ, Hollinshead, M, Holmes, AJ, Homuth, G, Hoogman, M, Hong, LE, Hosten, N, Hottenga, J-J, Pol, HEH, Hwang, KS, Jack, CR, Jenkinson, M, Johnston, C, Joensson, EG, Kahn, RS, Kasperaviciute, D, Kelly, S, Kim, S, Kochunov, P, Koenders, L, Kraemer, B, Kwok, JBJ, Lagopoulos, J, Laje, G, Landen, M, Landman, BA, Lauriello, J, Lawrie, SM, Lee, PH, Le Hellard, S, Lemaitre, H, Leonardo, CD, Li, C-S, Liberg, B, Liewald, DC, Liu, X, Lopez, LM, Loth, E, Lourdusamy, A, Luciano, M, Macciardi, F, Machielsen, MWJ, MacQueen, GM, Malt, UF, Mandl, R, Manoach, DS, Martinot, J-L, Matarin, M, Mather, KA, Mattheisen, M, Mattingsdal, M, Meyer-Lindenberg, A, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Meisenzahl, E, Melle, I, Milaneschi, Y, Mohnke, S, Montgomery, GW, Morris, DW, Moses, EK, Mueller, BA, Munoz Maniega, S, Muehleisen, TW, Mueller-Myhsok, B, Mwangi, B, Nauck, M, Nho, K, Nichols, TE, Nilsson, L-G, Nugent, AC, Nyberg, L, Olvera, RL, Oosterlaan, J, Ophoff, RA, Pandolfo, M, Papalampropoulou-Tsiridou, M, Papmeyer, M, Paus, T, Pausova, Z, Pearlson, GD, Penninx, BW, Peterson, CP, Pfennig, A, Phillips, M, Pike, GB, Poline, J-B, Potkin, SG, Puetz, B, Ramasamy, A, Rasmussen, J, Rietschel, M, Rijpkema, M, Risacher, SL, Roffman, JL, Roiz-Santianez, R, Romanczuk-Seiferth, N, Rose, EJ, Royle, NA, Rujescu, D, Ryten, M, Sachdev, PS, Salami, A, Satterthwaite, TD, Savitz, J, Saykin, AJ, Scanlon, C, Schmaal, L, Schnack, HG, Schork, AJ, Schulz, SC, Schuer, R, Seidman, L, Shen, L, Shoemaker, JM, Simmons, A, Sisodiya, SM, Smith, C, Smoller, JW, Soares, JC, Sponheim, SR, Sprooten, E, Starr, JM, Steen, VM, Strakowski, S, Strike, L, Sussmann, J, Saemann, PG, Teumer, A, Toga, AW, Tordesillas-Gutierrez, D, Trabzuni, D, Trost, S, Turner, J, Van den Heuvel, M, van der Wee, NJ, van Eijk, K, van Erp, TGM, van Haren, NEM, van 't Ent, D, van Tol, M-J, Hernandez, MCV, Veltman, DJ, Versace, A, Voelzke, H, Walker, R, Walter, H, Wang, L, Wardlaw, JM, Weale, ME, Weiner, MW, Wen, W, Westlye, LT, Whalley, HC, Whelan, CD, White, T, Winkler, AM, Wittfeld, K, Woldehawariat, G, Wolf, C, Zilles, D, Zwiers, MP, Thalamuthu, A, Schofield, PR, Freimer, NB, Lawrence, NS, and Drevets, W
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
Published: 2014

32. The role of adiposity in cardiometabolic traits: a mendelian randomization analysis

Author: Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, Prokopenko, I., Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, and Prokopenko, I.
Abstract: Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (
Published: 2013

33. A new regulatory variant in the interleukin-6 receptor gene associates with asthma risk

Author: Revez, JA, Bain, L, Chapman, B, Powell, JE, Jansen, R, Duffy, DL, Tung, JY, Penninx, BW, Visscher, PM, De Geus, EJC, Boomsma, DI, Hinds, DA, Martin, NG, Montgomery, GW, Ferreira, MAR, Revez, JA, Bain, L, Chapman, B, Powell, JE, Jansen, R, Duffy, DL, Tung, JY, Penninx, BW, Visscher, PM, De Geus, EJC, Boomsma, DI, Hinds, DA, Martin, NG, Montgomery, GW, and Ferreira, MAR
Abstract: The main genetic determinant of soluble interleukin 6 receptor (sIL-6R) levels is the missense variant rs2228145 that maps to the cleavage site of IL-6R. For each Ala allele, sIL-6R serum levels increase by ≈ 20 ng ml(-1) and asthma risk by 1.09-fold. However, this variant does not explain the total heritability for sIL-6R levels. Additional independent variants in IL6R may therefore contribute to variation in sIL-6R levels and influence asthma risk. We imputed 471 variants in IL6R and tested these for association with sIL-6R serum levels in 360 individuals. An intronic variant (rs12083537) was associated with sIL-6R levels independently of rs4129267 (P=0.0005), a proxy single-nucleotide polymorphism for rs2228145. A significant and consistent association for rs12083537 was observed in a replication panel of 354 individuals (P=0.033). Each rs12083537:A allele increased sIL-6R serum levels by 2.4 ng ml(-1). Analysis of mRNA levels in two cohorts did not identify significant associations between rs12083537 and IL6R transcription levels. On the other hand, results from 16,705 asthmatics and 30,809 controls showed that the rs12083537:A allele increased asthma risk by 1.04-fold (P=0.0419). Genetic risk scores based on IL6R regulatory variants may prove useful in explaining variation in clinical response to tocilizumab, an anti-IL-6R monoclonal antibody.
Published: 2013

34. Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort

Author: Verbeek, EC, Bevova, MR, Bochdanovits, Z, Rizzu, P, Bakker, IMC, Uithuisje, T, de Geus, EJ, Smit, JH, Penninx, BW, Boomsma, DI, Hoogendijk, Witte, Heutink, P, Verbeek, EC, Bevova, MR, Bochdanovits, Z, Rizzu, P, Bakker, IMC, Uithuisje, T, de Geus, EJ, Smit, JH, Penninx, BW, Boomsma, DI, Hoogendijk, Witte, and Heutink, P
Abstract: Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS mapped to a region spanning the gene PCLO, and the non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort and performed association analysis to investigate if rs2522833 is the causal variant or simply in linkage disequilibrium with a more associated variant. GRM7 and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort. After next generation sequencing and association analysis we excluded the possibility of an undetected common variant to be more associated. For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07) than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide significance was found. Although we did not take into account rare variants, we conclude that our results provide further support for the hypothesis that the non-synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the causal variant in the GAIN-MDD cohort.
Published: 2013

35. Modulatory Effects of the Piccolo Genotype on Emotional Memory in Health and Depression

Author: Woudstra, S, van Tol, MJ, Bochdanovits, Z, van der Wee, NJ, Zitman, FG, van Buchem, MA, Opmeer, EM, Aleman, A, Penninx, BW, Veltman, DJ, Hoogendijk, Witte, Woudstra, S, van Tol, MJ, Bochdanovits, Z, van der Wee, NJ, Zitman, FG, van Buchem, MA, Opmeer, EM, Aleman, A, Penninx, BW, Veltman, DJ, and Hoogendijk, Witte
Published: 2013

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

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

37. Genome-wide meta-analysis of common variant differences between men and women

Author: Boraska, V, Jeroncic, A, Colonna, V, Southam, L, Nyholt, DR, Rayner, NW, Perry, JRB, Toniolo, D, Albrecht, E, Ang, W, Bandinelli, S, Barbalic, M, Barroso, I, Beckmann, JS, Biffar, R, Boomsma, D, Campbell, H, Corre, T, Erdmann, J, Esko, T, Fischer, K (Kirsten), Franceschini, N, Frayling, TM, Girotto, G, Gonzalez, JR, Harris, TB, Heath, AC, Heid, IM, Hoffmann, W, Hofman, Bert, Horikoshi, M, Zhao, JH, Jackson, AU, Hottenga, JJ (Jouke Jan), Jula, A, Kahonen, M, Khaw, KT, Kiemeney, LA, Klopp, N, Kutalik, Z, Lagou, V, Launer, LJ (Lenore), Lehtimaki, T, Lemire, M, Lokki, ML, Loley, C, Luan, JA, Mangino, M, Leach, IM, Medland, SE, Mihailov, E, Montgomery, GW, Navis, G, Newnham, J, Nieminen, MS, Palotie, A, Panoutsopoulou, K, Peters, A, Pirastu, N, Polasek, O, Rehnstrom, K, Ripatti, S, Ritchie, GRS, Rivadeneira, Fernando, Robino, A, Samani, NJ, Shin, SY, Sinisalo, J, Smit, JH, Soranzo, N, Stolk, Lisette, Swinkels, DW, Tanaka, T, Teumer, A, Tonjes, A, Traglia, M, Tuomilehto, J, Valsesia, A, van Gilst, WH, van Meurs, Joyce, Smith, AV, Viikari, J, Vink, JM, Waeber, G, Warrington, NM, Widen, E, Willemsen, G, Wright, AF, Zanke, BW, Zgaga, L, Boehnke, M, d'Adamo, AP, de Geus, ED, Demerath, EW, Heijer, Mariska, Eriksson, JG, Ferrucci, L, Gieger, C, Gudnason, V, Hayward, C, Hengstenberg, C, Hudson, TJ, Jarvelin, MR, Kogevinas, M, Loos, RJF, Martin, NG, Metspalu, A, Pennell, CE, Penninx, BW, Perola, M, Raitakari, O, Salomaa, V, Schreiber, S, Schunkert, H, Spector, TD, Stumvoll, M, Uitterlinden, André, Ulivi, S, van der Harst, P, Vollenweider, P, Volzke, H, Wareham, NJ, Wichmann, HE, Wilson, JF, Rudan, I, Xue, YL, Zeggini, E, Boraska, V, Jeroncic, A, Colonna, V, Southam, L, Nyholt, DR, Rayner, NW, Perry, JRB, Toniolo, D, Albrecht, E, Ang, W, Bandinelli, S, Barbalic, M, Barroso, I, Beckmann, JS, Biffar, R, Boomsma, D, Campbell, H, Corre, T, Erdmann, J, Esko, T, Fischer, K (Kirsten), Franceschini, N, Frayling, TM, Girotto, G, Gonzalez, JR, Harris, TB, Heath, AC, Heid, IM, Hoffmann, W, Hofman, Bert, Horikoshi, M, Zhao, JH, Jackson, AU, Hottenga, JJ (Jouke Jan), Jula, A, Kahonen, M, Khaw, KT, Kiemeney, LA, Klopp, N, Kutalik, Z, Lagou, V, Launer, LJ (Lenore), Lehtimaki, T, Lemire, M, Lokki, ML, Loley, C, Luan, JA, Mangino, M, Leach, IM, Medland, SE, Mihailov, E, Montgomery, GW, Navis, G, Newnham, J, Nieminen, MS, Palotie, A, Panoutsopoulou, K, Peters, A, Pirastu, N, Polasek, O, Rehnstrom, K, Ripatti, S, Ritchie, GRS, Rivadeneira, Fernando, Robino, A, Samani, NJ, Shin, SY, Sinisalo, J, Smit, JH, Soranzo, N, Stolk, Lisette, Swinkels, DW, Tanaka, T, Teumer, A, Tonjes, A, Traglia, M, Tuomilehto, J, Valsesia, A, van Gilst, WH, van Meurs, Joyce, Smith, AV, Viikari, J, Vink, JM, Waeber, G, Warrington, NM, Widen, E, Willemsen, G, Wright, AF, Zanke, BW, Zgaga, L, Boehnke, M, d'Adamo, AP, de Geus, ED, Demerath, EW, Heijer, Mariska, Eriksson, JG, Ferrucci, L, Gieger, C, Gudnason, V, Hayward, C, Hengstenberg, C, Hudson, TJ, Jarvelin, MR, Kogevinas, M, Loos, RJF, Martin, NG, Metspalu, A, Pennell, CE, Penninx, BW, Perola, M, Raitakari, O, Salomaa, V, Schreiber, S, Schunkert, H, Spector, TD, Stumvoll, M, Uitterlinden, André, Ulivi, S, van der Harst, P, Vollenweider, P, Volzke, H, Wareham, NJ, Wichmann, HE, Wilson, JF, Rudan, I, Xue, YL, and Zeggini, E
Abstract: The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency 0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P 5 10(8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across approximate to 115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.
Published: 2012

38. A Fine-Mapping Study of 7 Top Scoring Genes from a GWAS for Major Depressive Disorder

Author: Verbeek, EC, Bakker, IMC, Bevova, MR, Bochdanovits, Z, Rizzu, P, Sondervan, D, Willemsen, G, de Geus, EJ, Smit, JH, Penninx, BW, Boomsma, DI, Hoogendijk, Witte, Heutink, P, Verbeek, EC, Bakker, IMC, Bevova, MR, Bochdanovits, Z, Rizzu, P, Sondervan, D, Willemsen, G, de Geus, EJ, Smit, JH, Penninx, BW, Boomsma, DI, Hoogendijk, Witte, and Heutink, P
Abstract: Major depressive disorder (MDD) is a psychiatric disorder that is characterized -amongst others- by persistent depressed mood, loss of interest and pleasure and psychomotor retardation. Environmental circumstances have proven to influence the aetiology of the disease, but MDD also has an estimated 40% heritability, probably with a polygenic background. In 2009, a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. A non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became only nominally significant after post-hoc analysis with an Australian cohort which used similar ascertainment. The absence of genome-wide significance may be caused by low SNP coverage of genes. To increase SNP coverage to 100% for common variants (m.a.f > 0.1, r(2)> 0.8), we selected seven genes from the GAIN-MDD GWAS: PCLO, GZMK, ANPEP, AFAP1L1, ST3GAL6, FGF14 and PTK2B. We genotyped 349 SNPs and obtained the lowest P-value for rs2715147 in PCLO at P=6.8E-7. We imputed, filling in missing genotypes, after which rs2715147 and rs2715148 showed the lowest P-value at P=1.2E-6. When we created a haplotype of these SNPs together with the non-synonymous coding SNP rs2522833, the P-value decreased to P=9.9E-7 but was not genome wide significant. Although our study did not identify a more strongly associated variant, the results for PCLO suggest that the causal variant is in high LD with rs2715147, rs2715148 and rs2522833.
Published: 2012

39. Piccolo genotype modulates neural correlates of emotion processing but not executive functioning

Author: Woudstra, S, Bochdanovits, Z, van Tol, MJ, Veltman, DJ, Zitman, FG, van Buchem, MA, van der Wee, NJ, Opmeer, EM, Demenescu, LR, Aleman, A, Penninx, BW, Hoogendijk, Witte, Woudstra, S, Bochdanovits, Z, van Tol, MJ, Veltman, DJ, Zitman, FG, van Buchem, MA, van der Wee, NJ, Opmeer, EM, Demenescu, LR, Aleman, A, Penninx, BW, and Hoogendijk, Witte
Abstract: Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene-involved in monoaminergic neurotransmission-as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging ( fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD. Translational Psychiatry (2012) 2, e99; doi:10.1038/tp.2012.29; published online 3 April 2012
Published: 2012

40. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma

Author: Chambers, JC, Zhang, WH, Sehmi, J, Li, XZ, Wass, MN, van der Harst, P, Holm, H, Sanna, S, Kavousi, Maryam, Baumeister, SE, Coin, LJ, Deng, GH, Gieger, C, Heard-Costa, NL, Hottenga, JJ (Jouke Jan), Kuhnel, B, Kumar, V, Lagou, V, Liang, LM, Luan, JA, Vidal, PM, Leach, IM, O'Reilly, PF, Peden, JF, Rahmioglu, N, Soininen, P, Speliotes, EK, Yuan, X, Thorleifsson, G, Alizadeh, BZ, Atwood, LD, Borecki, IB, Brown, MJ, Charoen, P, Cucca, F, Das, Devashish, de Geus, EJC, Dixon, AL, Doering, A, Ehret, G, Eyjolfsson, GI, Farrall, M, Forouhi, NG, Friedrich, N, Goessling, W, Gudbjartsson, DF, Harris, TB, Hartikainen, AL, Heath, S, Hirschfield, GM, Hofman, Bert, Homuth, G, Hypponen, E, Janssen, HLA, Johnson, T, Kangas, AJ, Kema, IP, Kuhn, JP, Lai, S, Lathrop, M, Lerch, MM, Li, Yunlei, Liang, TJ, Lin, JP, Loos, RJF, Martin, NG, Moffatt, MF, Montgomery, GW, Munroe, PB, Musunuru, K, Nakamura, Y, O'Donnell, CJ, Olafsson, I, Penninx, BW, Pouta, A, Prins, BP, Prokopenko, I, Puls, R, Ruokonen, A, Savolainen, MJ, Schlessinger, D, Schouten, Jeoffrey, Seedorf, U, Sen-Chowdhry, S, Siminovitch, KA, Smit, JH, Spector, TD, Tan, WT, Teslovich, TM, Tukiainen, T, Uitterlinden, André, van der Klauw, MM (Melanie), Vasan, RS, Wallace, C, Wallaschofski, H, Wichmann, HE, Willemsen, G, Wurtz, P, Xu, C, Yerges-Armstrong, LM, Abecasis, GR, Ahmadi, KR, Boomsma, DI, Caulfield, M, Cookson, WO, Duijn, Cornelia, Froguel, P, Matsuda, K, McCarthy, MI, Meisinger, C, Mooser, V, Pietilainen, KH, Schumann, G, Snieder, H, Sternberg, MJE, Stolk, RP (Ronald), Thomas, HC, Thorsteinsdottir, U, Uda, M, Waeber, G, Wareham, NJ, Waterworth, DM, Watkins, H, Whitfield, JB, Witteman, JCM, Wolffenbuttel, BHR, Fox, CS, Ala-Korpela, M, Stefansson, K, Vollenweider, P, Volzke, H, Schadt, EE, Scott, J, Jarvelin, MR, Elliott, P, Kooner, JS, Chambers, JC, Zhang, WH, Sehmi, J, Li, XZ, Wass, MN, van der Harst, P, Holm, H, Sanna, S, Kavousi, Maryam, Baumeister, SE, Coin, LJ, Deng, GH, Gieger, C, Heard-Costa, NL, Hottenga, JJ (Jouke Jan), Kuhnel, B, Kumar, V, Lagou, V, Liang, LM, Luan, JA, Vidal, PM, Leach, IM, O'Reilly, PF, Peden, JF, Rahmioglu, N, Soininen, P, Speliotes, EK, Yuan, X, Thorleifsson, G, Alizadeh, BZ, Atwood, LD, Borecki, IB, Brown, MJ, Charoen, P, Cucca, F, Das, Devashish, de Geus, EJC, Dixon, AL, Doering, A, Ehret, G, Eyjolfsson, GI, Farrall, M, Forouhi, NG, Friedrich, N, Goessling, W, Gudbjartsson, DF, Harris, TB, Hartikainen, AL, Heath, S, Hirschfield, GM, Hofman, Bert, Homuth, G, Hypponen, E, Janssen, HLA, Johnson, T, Kangas, AJ, Kema, IP, Kuhn, JP, Lai, S, Lathrop, M, Lerch, MM, Li, Yunlei, Liang, TJ, Lin, JP, Loos, RJF, Martin, NG, Moffatt, MF, Montgomery, GW, Munroe, PB, Musunuru, K, Nakamura, Y, O'Donnell, CJ, Olafsson, I, Penninx, BW, Pouta, A, Prins, BP, Prokopenko, I, Puls, R, Ruokonen, A, Savolainen, MJ, Schlessinger, D, Schouten, Jeoffrey, Seedorf, U, Sen-Chowdhry, S, Siminovitch, KA, Smit, JH, Spector, TD, Tan, WT, Teslovich, TM, Tukiainen, T, Uitterlinden, André, van der Klauw, MM (Melanie), Vasan, RS, Wallace, C, Wallaschofski, H, Wichmann, HE, Willemsen, G, Wurtz, P, Xu, C, Yerges-Armstrong, LM, Abecasis, GR, Ahmadi, KR, Boomsma, DI, Caulfield, M, Cookson, WO, Duijn, Cornelia, Froguel, P, Matsuda, K, McCarthy, MI, Meisinger, C, Mooser, V, Pietilainen, KH, Schumann, G, Snieder, H, Sternberg, MJE, Stolk, RP (Ronald), Thomas, HC, Thorsteinsdottir, U, Uda, M, Waeber, G, Wareham, NJ, Waterworth, DM, Watkins, H, Whitfield, JB, Witteman, JCM, Wolffenbuttel, BHR, Fox, CS, Ala-Korpela, M, Stefansson, K, Vollenweider, P, Volzke, H, Schadt, EE, Scott, J, Jarvelin, MR, Elliott, P, and Kooner, JS
Abstract: Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.
Published: 2011

41. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, Hirschhorn, JN, Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, and Hirschhorn, JN
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can ide
Published: 2010

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

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

43. Longitudinal relationship of depressive and anxiety symptoms with dyslipidemia and abdominal obesity.

Author: van Reedt Dortland AK, Giltay EJ, van Veen T, Zitman FG, and Penninx BW
Published: 2013
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44. Two-year course of depressive and anxiety disorders: Results from the Netherlands Study of Depression and Anxiety (NESDA)

Author: Penninx BW, Nolen WA, Lamers F, Zitman FG, Smit JH, Spinhoven P, Cuijpers P, de Jong PJ, van Marwijk HW, der Meer K, Verhaak P, Laurant MG, de Graaf R, Hoogendijk WJ, der Wee N, Ormel J, van Dyck R, and Beekman AT
Published: 2011
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45. The effects of neuroticism, extraversion, and positive and negative life events on a one-year course of depressive symptoms in euthymic previously depressed patients versus healthy controls.

Author: Spinhoven P, Elzinga B, Roelofs K, Hovens JG, van Oppen P, Zitman FG, and Penninx BW
Published: 2011
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46. Symptom dimensions of depression and anxiety and the metabolic syndrome.

Author: Luppino FS, van Reedt Dortland AK, Wardenaar KJ, Bouvy PF, Giltay EJ, Zitman FG, and Penninx BW
Published: 2011
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47. Genome-wide association study of suicide attempts in mood disorder patients.

Author: Perlis RH, Huang J, Purcell S, Fava M, Rush AJ, Sullivan PF, Hamilton SP, McMahon FJ, Schulze T, Potash JB, Zandi PP, Willour VL, Penninx BW, Boomsma DI, Vogelzangs N, Middeldorp CM, Rietschel M, Nöthen M, Cichon S, and Gurling H
Abstract: Objective: Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts.Method: The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort.Results: Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety.Conclusions: The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation. [ABSTRACT FROM AUTHOR]
Published: 2010
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48. The shared genetics of migraine and anxious depression.

Author: Ligthart L, Nyholt DR, Penninx BW, and Boomsma DI
Abstract: Objectives.--To investigate (1) whether shared genetic factors influence migraine and anxious depression; (2) whether the genetic architecture of migraine depends on anxious depression; (3) whether the association between migraine and anxious depression is causal.Background.--Migraine and anxious depression frequently occur together, but little is known about the mechanisms causing this association.Methods.--A twin study was conducted to model the genetic architecture of migraine and anxious depression and the covariance between them. Anxious depression was also added to the model as a moderator variable to examine whether anxious depression affects the genetic architecture of migraine. Causal models were explored with the co-twin control method.Results.--Modest but significant phenotypic (rP = 0.28), genetic (rG = 0.30), and nonshared environmental (rE = 0.26) correlations were found between the 2 traits. Interestingly, the heritability of migraine depended on the level of anxious depression: the higher the anxious depression score, the lower the relative contribution of genetic factors to the individual differences in migraine susceptibility. The observed risk patterns in discordant twins are most consistent with a bidirectional causal relationship.Conclusions.--These findings confirm the genetic association between migraine and anxious depression and are consistent with a syndromic association between the 2 traits. This highlights the importance of taking comorbidity into account in genetic studies of migraine, especially in the context of selection for large-scale genotyping efforts. Genetic studies may be most effective when migraine with and without comorbid anxious depression are treated as separate phenotypes. [ABSTRACT FROM AUTHOR]
Published: 2010
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49. Presence of comorbid somatic disorders among patients referred to mental health care in the Netherlands.

Author: Van der Feltz-Cornelis CM, Ten Have M, Penninx BW, Beekman AT, Smit JH, De Graaf R, Van der Feltz-Cornelis, Christina M, Ten Have, Margreet, Penninx, Brenda W, Beekman, Aartjan T F, Smit, Jan H, and De Graaf, Ron
Abstract: Objective: Referral to mental health care was examined among persons with mental disorders with and without comorbid somatic conditions to determine whether certain conditions may make detection of mental disorders by primary care physicians more or less likely.Methods: Receipt of mental health care in the primary and specialty care settings by respondents to the Netherlands Mental Health Survey and Incidence Study who had mood disorders (N=573), anxiety disorders (N=912), and substance use disorders (N=533) was examined, first broadly by any of 31 somatic conditions and then by each of the five most common conditions.Results: Broadly, those with anxiety disorders and a somatic condition were more likely to use care in both settings (adjusted relative risk ratios [RRRs]=1.75 and 1.58 for primary and specialty care, respectively), and those with substance use disorders and a somatic condition were more likely to use specialty care (RRR=2.15). More narrowly, use of specialty care by persons with mood disorders was three times as likely for those with rheumatoid arthritis or a digestive tract disorder (RRRs=3.04 and 2.92). For anxiety disorders, specialty care was more likely for those with chronic backache (RRR=2.14) or a digestive tract disorder (RRR=3.56). For substance use disorders, those with chronic backache were six times as likely to use specialty care (RRR=6.05) and those with a digestive tract disorder were three times as likely (RRR=3.09).Conclusions: Poor somatic health in general seemed to increase the likelihood of use of mental health care for persons with anxiety or substance use disorders, but not for those with mood disorders. Having certain somatic conditions appeared to enhance recognition and treatment of three common mental disorders. [ABSTRACT FROM AUTHOR]
Published: 2010
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50. Salivary cortisol levels in persons with and without different anxiety disorders.

Author: Vreeburg SA, Zitman FG, van Pelt J, Derijk RH, Verhagen JC, van Dyck R, Hoogendijk WJ, Smit JH, and Penninx BW
Published: 2010
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