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2. POS0224 PRIMARY OSTEOARTHRITIS CHONDROCYTE MAP OF CHROMATIN CONFORMATION REVEALS NOVEL EFFECTOR GENES

Author

Bittner, N., primary, Shi, C., additional, Zhao, D., additional, Ding, J., additional, Southam, L., additional, Swift, D., additional, Kreitmaier, P., additional, Tutino, M., additional, Stergiou, O., additional, Cheung, J., additional, Katsoula, G., additional, Hankinson, J., additional, Wilkinson, M., additional, Orozco, G., additional, and Zeggini, E., additional

Published
2024
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3. A genome-wide association study of anorexia nervosa

Author

Boraska, V, Franklin, CS, Floyd, JAB, Thornton, LM, Huckins, LM, Southam, L, Rayner, NW, Tachmazidou, I, Klump, KL, Treasure, J, Lewis, CM, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, RAH, Kas, MJH, Favaro, A, Santonastaso, P, Fernández-Aranda, F, Gratacos, M, Rybakowski, F, Dmitrzak-Weglarz, M, Kaprio, J, Keski-Rahkonen, A, Raevuori, A, Van Furth, EF, Slof-Op 't Landt, MCT, Hudson, JI, Reichborn-Kjennerud, T, Knudsen, GPS, Monteleone, P, Kaplan, AS, Karwautz, A, Hakonarson, H, Berrettini, WH, Guo, Y, Li, D, Schork, NJ, Komaki, G, Ando, T, Inoko, H, Esko, T, Fischer, K, Männik, K, Metspalu, A, Baker, JH, Cone, RD, Dackor, J, DeSocio, JE, Hilliard, CE, O'Toole, JK, Pantel, J, Szatkiewicz, JP, Taico, C, Zerwas, S, Trace, SE, Davis, OSP, Helder, S, Bühren, K, Burghardt, R, de Zwaan, M, Egberts, K, Ehrlich, S, Herpertz-Dahlmann, B, Herzog, W, Imgart, H, Scherag, A, Scherag, S, Zipfel, S, Boni, C, Ramoz, N, Versini, A, Brandys, MK, Danner, UN, de Kovel, C, Hendriks, J, Koeleman, BPC, Ophoff, RA, Strengman, E, van Elburg, AA, Bruson, A, Clementi, M, Degortes, D, Forzan, M, Tenconi, E, Docampo, E, Escaramís, G, Jiménez-Murcia, S, Lissowska, J, Rajewski, A, Szeszenia-Dabrowska, N, Slopien, A, Hauser, J, Karhunen, L, Meulenbelt, I, Slagboom, PE, Tortorella, A, and Maj, M

Subjects
Anorexia, Mental Health, Serious Mental Illness, Human Genome, Eating Disorders, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Anorexia Nervosa, Asian People, Calcineurin, Carrier Proteins, Case-Control Studies, Cullin Proteins, Female, Genome-Wide Association Study, Guanine Nucleotide Exchange Factors, Humans, Japan, Male, Meta-Analysis as Topic, Nuclear Proteins, Polymorphism, Single Nucleotide, White People, anorexia nervosa, body mass index, eating disorders, genome-wide association study, GWAS, metabolic, Wellcome Trust Case Control Consortium 3, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Published
2014

4. Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study

Author

Panoutsopoulou, K, Southam, L, Elliott, KS, Wrayner, N, Zhai, G, Beazley, C, Thorleifsson, G, Arden, NK, Carr, A, Chapman, K, Deloukas, P, Doherty, M, McCaskie, A, Ollier, WER, Ralston, SH, Spector, TD, Valdes, AM, Wallis, GA, Wilkinson, JM, Arden, E, Battley, K, Blackburn, H, Blanco, FJ, Bumpstead, S, Cupples, LA, Day-Williams, AG, Dixon, K, Doherty, SA, Esko, T, Evangelou, E, Felson, D, Gomez-Reino, JJ, Gonzalez, A, Gordon, A, Gwilliam, R, Halldorsson, BV, Hauksson, VB, Hofman, A, Hunt, SE, Ioannidis, JPA, Ingvarsson, T, Jonsdottir, I, Jonsson, H, Keen, R, Kerkhof, HJM, Kloppenburg, MG, Koller, N, Lakenberg, N, Lane, NE, Lee, AT, Metspalu, A, Meulenbelt, I, Nevitt, MC, O'Neill, F, Parimi, N, Potter, SC, Rego-Perez, I, Riancho, JA, Sherburn, K, Slagboom, PE, Stefansson, K, Styrkarsdottir, U, Sumillera, M, Swift, D, Thorsteinsdottir, U, Tsezou, A, Uitterlinden, AG, van Meurs, JBJ, Watkins, B, Wheeler, M, Mitchell, S, Zhu, Y, Zmuda, JM, Consortium, arcOGEN, Zeggini, E, and Loughlin, J

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Arthritis, Genetics, Prevention, Aging, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Osteoarthritis, Hip, Osteoarthritis, Knee, Polymorphism, Single Nucleotide, arcOGEN Consortium, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectivesThe genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis.MethodsThe authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44,449 individuals), and de novo in 14 534 independent samples, all of European descent.ResultsNone of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects.ConclusionsIdentifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.

Published
2011

7. A GENOME WIDE ASSOCIATION STUDY OF DXA-DERIVED MINIMUM JOINT SPACE WIDTH OF THE HIP PROVIDES FURTHER INSIGHTS INTO ITS GENETIC ARCHITECTURE: FINDINGS FROM UK BIOBANK

Author

Faber, B., primary, Frysz, M., additional, Ebsim, R., additional, Lundberg, M., additional, Southam, L., additional, Hartley, A., additional, Saunders, F.R., additional, Lindner, C., additional, Gregory, J.S., additional, Aspden, R.M., additional, Harvey, N.C., additional, Zeggini, E., additional, Smith, G. Davey, additional, Cootes, T., additional, Kemp, J.P., additional, and Tobias, J.H., additional

Published
2022
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9. AN EPIGENOME-WIDE VIEW OF OSTEOARTHRITIS IN PRIMARY TISSUES

Author

Kreitmaier, P., primary, Suderman, M., additional, Southam, L., additional, Coutinho de Almeida, R., additional, Hatzikotoulas, K., additional, Meulenbelt, I., additional, Steinberg, J., additional, Relton, C., additional, Wilkinson, J.M., additional, and Zeggini, E., additional

Published
2022
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10. Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology

Author

Bjornsdottir, G. Stefansdottir, L. Thorleifsson, G. Sulem, P. Norland, K. Ferkingstad, E. Oddsson, A. Zink, F. Lund, S.H. Nawaz, M.S. Bragi Walters, G. Skuladottir, A.T. Gudjonsson, S.A. Einarsson, G. Halldorsson, G.H. Bjarnadottir, V. Sveinbjornsson, G. Helgadottir, A. Styrkarsdottir, U. Gudmundsson, L.J. Pedersen, O.B. Hansen, T.F. Werge, T. Banasik, K. Troelsen, A. Skou, S.T. Thørner, L.W. Erikstrup, C. Nielsen, K.R. Mikkelsen, S. Andersen, S. Brunak, S. Burgdorf, K. Hjalgrim, H. Jemec, G. Jennum, P. Johansson, P.I. Nielsen, K.R. Nyegaard, M. Bruun, M.T. Pedersen, O.B. Dinh, K.M. Sørensen, E. Ostrowski, S. Johansson, P.I. Gudbjartsson, D. Stefánsson, H. Þorsteinsdóttir, U. Larsen, M.A.H. Didriksen, M. Sækmose, S. Zeggini, E. Hatzikotoulas, K. Southam, L. Gilly, A. Barysenka, A. van Meurs, J.B.J. Boer, C.G. Uitterlinden, A.G. Styrkársdóttir, U. Stefánsdóttir, L. Jonsson, H. Ingvarsson, T. Esko, T. Mägi, R. Teder-Laving, M. Ikegawa, S. Terao, C. Takuwa, H. Meulenbelt, I. Coutinho de Almeida, R. Kloppenburg, M. Tuerlings, M. Slagboom, P.E. Nelissen, R.R.G.H.H. Valdes, A.M. Mangino, M. Tsezou, A. Zengini, E. Alexiadis, G. Babis, G.C. Cheah, K.S.E. Wu, T.T. Samartzis, D. Cheung, J.P.Y. Sham, P.C. Kraft, P. Kang, J.H. Hveem, K. Zwart, J.-A. Luetge, A. Skogholt, A.H. Johnsen, M.B. Thomas, L.F. Winsvold, B. Gabrielsen, M.E. Lee, M.T.M. Zhang, Y. Lietman, S.A. Shivakumar, M. Smith, G.D. Tobias, J.H. Hartley, A. Gaunt, T.R. Zheng, J. Wilkinson, J.M. Steinberg, J. Morris, A.P. Jonsdottir, I. Bjornsson, A. Olafsson, I.H. Ulfarsson, E. Blondal, J. Vikingsson, A. Brunak, S. Ostrowski, S.R. Ullum, H. Thorsteinsdottir, U. Stefansson, H. Gudbjartsson, D.F. Thorgeirsson, T.E. Stefansson, K. DBDS Genetic Consortium GO Consortium

Abstract

Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10−39; ORdorsalgia = 0.92, P = 7.2 × 10−15) is with a 3’UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 − 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10−11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes. © 2022, The Author(s).

Published
2022

11. Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L M, Hatzikotoulas, K, Southam, L, Thornton, L M, Steinberg, J, Aguilera-McKay, F, Treasure, J, Schmidt, U, Gunasinghe, C, Romero, A, Curtis, C, Rhodes, D, Moens, J, Kalsi, G, Dempster, D, Leung, R, Keohane, A, Burghardt, R, Ehrlich, S, Hebebrand, J, Hinney, A, Ludolph, A, Walton, E, Deloukas, P, Hofman, A, Palotie, A, Palta, P, van Rooij, F J A, Stirrups, K, Adan, R, Boni, C, Cone, R, Dedoussis, G, van Furth, E, Gonidakis, F, Gorwood, P, Hudson, J, Kaprio, J, Kas, M, Keski-Rahonen, A, Kiezebrink, K, Knudsen, G-P, Maj, M, Monteleone, A M, Monteleone, P, Raevuori, A H, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, van Elburg, A, Collier, D A, Sullivan, P F, Breen, G, Bulik, C M, and Zeggini, E

Published
2018
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12. The power of genetic diversity in genome-wide association studies of lipids

Author

Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), Willer, C. J. (Cristen J.), Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), and Willer, C. J. (Cristen J.)

Abstract

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4‐23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.

Published
2021

13. The trans-ancestral genomic architecture of glycemic traits

Author

Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), Barroso, I. (Ines), Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), and Barroso, I. (Ines)

Abstract

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

Published
2021

14. Genome-wide association of phenotypes based on clustering patterns of hand osteoarthritis identify WNT9A as novel osteoarthritis gene

Author

Boer, Cindy, Yau, MS, Rice, SJ, Almeida, R, Cheung, K, Styrkarsdottir, U, Southam, L, Broer, Linda, Wilkinson, JM, Uitterlinden, André, Zeggini, E, Felson, D, Loughlin, J, Young, M, Capellini, TD, Meulenbelt, I, van Meurs, Joyce, Boer, Cindy, Yau, MS, Rice, SJ, Almeida, R, Cheung, K, Styrkarsdottir, U, Southam, L, Broer, Linda, Wilkinson, JM, Uitterlinden, André, Zeggini, E, Felson, D, Loughlin, J, Young, M, Capellini, TD, Meulenbelt, I, and van Meurs, Joyce

Abstract

Background Despite recent advances in the understanding of the genetic architecture of osteoarthritis (OA), only two genetic loci have been identified for OA of the hand, in part explained by the complexity of the different hand joints and heterogeneity of OA pathology. Methods We used data from the Rotterdam Study (RSI, RSII and RSIII) to create three hand OA phenotypes based on clustering patterns of radiographic OA severity to increase power in our modest discovery genome-wide association studies in the RS (n=8700), and sought replication in an independent cohort, the Framingham Heart Study (n=1203). We used multiple approaches that leverage different levels of information and functional data to further investigate the underlying biological mechanisms and candidate genes for replicated loci. We also attempted to replicate known OA loci at other joint sites, including the hips and knees. Results We found two novel genome-wide significant loci for OA in the thumb joints. We identified WNT9A as a possible novel causal gene involved in OA pathogenesis. Furthermore, several previously identified genetic loci for OA seem to confer risk for OA across multiple joints: TGFa, RUNX2, COL27A1, ASTN2, IL11 and GDF5 loci. Conclusions We identified a robust novel genetic locus for hand OA on chromosome 1, of which WNT9A is the most likely causal gene. In addition, multiple genetic loci were identified to be associated with OA across multiple joints. Our study confirms the potential for novel insight into the genetic architecture of OA by using biologically meaningful stratified phenotypes.

Published
2021

15. The trans-ancestral genomic architecture of glycemic traits

Author

Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), Tremoli E., Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), and Tremoli E.

Abstract

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

Published
2021

17. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (Nature Genetics, (2018), 50, 1, (26-41), 10.1038/s41588-017-0011-x)

Author

Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., Guo, X., Hendricks, A. E., Karaderi, T., Lempradl, A., Locke, A. E., Mahajan, A., Marouli, E., Sivapalaratnam, S., Young, K. L., Alfred, T., Feitosa, M. F., Masca, N. G. D., Manning, A. K., Medina-Gomez, C., Mudgal, P., M. C. Y., Ng, Reiner, A. P., Vedantam, S., Willems, S. M., Winkler, T. W., Abecasis, G., Aben, K. K., Alam, D. S., Alharthi, S. E., Marchiori, Allison, Amouyel, P., Asselbergs, F. W., Auer, P. L., Balkau, B., Bang, L. E., Barroso, I., Bastarache, L., Benn, M., Bergmann, S., Bielak, L. F., Bluher, M., Boehnke, M., Boeing, H., Boerwinkle, E., Boger, C. A., Bork-Jensen, J., Bots, M. L., Bottinger, E. P., Bowden, D. W., Brandslund, I., Breen, G., Brilliant, M. H., Broer, L., Brumat, M., Burt, A. A., Butterworth, A. S., Campbell, P. T., Cappellani, S., Carey, D. J., Catamo, E., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Chowdhury, R., Christensen, C., Chu, A. Y., Cocca, M., Collins, F. S., Cook, J. P., Corley, J., Galbany, J. C., Cox, A. J., Crosslin, D. S., Cuellar-Partida, G., D'Eustacchio, A., Danesh, J., Davies, G., Bakker, P. I. W., Groot, M. C. H., Mutsert, R., Deary, I. J., Dedoussis, G., Demerath, E. W., Heijer, M., Hollander, A. I., Ruijter, H. M., Dennis, J. G., Denny, J. C., Di Angelantonio, E., Drenos, F., Du, M., Dube, M. -P., Dunning, A. M., Easton, D. F., Edwards, T. L., Ellinghaus, D., Ellinor, P. T., Elliott, P., Evangelou, E., Farmaki, A. -E., Farooqi, I. S., Faul, J. D., Fauser, S., Feng, S., Ferrannini, E., Ferrieres, J., Florez, J. C., Ford, I., Fornage, M., Franco, O. H., Franke, A., Franks, P. W., Friedrich, N., Frikke-Schmidt, R., Galesloot, T. E., Gan, W., Gandin, I., Gasparini, P., Gibson, J., Giedraitis, V., Gjesing, A. P., Gordon-Larsen, P., Gorski, M., Grabe, H. -J., Grant, S. F. A., Grarup, N., Griffiths, H. L., Grove, M. L., Gudnason, V., Gustafsson, S., Haessler, J., Hakonarson, H., Hammerschlag, A. R., Hansen, T., Harris, K. M., Harris, T. B., Hattersley, A. T., Have, C. T., Hayward, C., He, L., Heard-Costa, N. L., Heath, A. C., Heid, I. M., Helgeland, O., Hernesniemi, J., Hewitt, A. W., Holmen, O. L., Hovingh, G. K., Howson, J. M. M., Hu, Y., Huang, P. L., Huffman, J. E., Ikram, M. A., Ingelsson, E., Jackson, A. U., Jansson, J. -H., Jarvik, G. P., Jensen, G. B., Jia, Y., Johansson, S., Jorgensen, M. E., Jorgensen, T., Jukema, J. W., Kahali, B., Kahn, R. S., Kahonen, M., Kamstrup, P. R., Kanoni, S., Kaprio, J., Karaleftheri, M., Kardia, S. L. R., Karpe, F., Kathiresan, S., Kee, F., Kiemeney, L. A., Kim, E., Kitajima, H., Komulainen, P., Kooner, J. S., Kooperberg, C., Korhonen, T., Kovacs, P., Kuivaniemi, H., Kutalik, Z., Kuulasmaa, K., Kuusisto, J., Laakso, M., Lakka, T. A., Lamparter, D., Lange, E. M., Lange, L. A., Langenberg, C., Larson, E. B., Lee, N. R., Lehtimaki, T., Lewis, C. E., Li, H., Li, J., Li-Gao, R., Lin, H., Lin, K. -H., Lin, L. -A., Lin, X., Lind, L., Lindstrom, J., Linneberg, A., Liu, C. -T., Liu, D. J., Liu, Y., K. S., Lo, Lophatananon, A., Lotery, A. J., Loukola, A., Luan, J., Lubitz, S. A., Lyytikainen, L. -P., Mannisto, S., Marenne, G., Mazul, A. L., Mccarthy, M. I., McKean-Cowdin, R., Medland, S. E., Meidtner, K., Milani, L., Mistry, V., Mitchell, P., Mohlke, K. L., Moilanen, L., Moitry, M., Montgomery, G. W., Mook-Kanamori, D. O., Moore, C., Mori, T. A., Morris, A. D., Morris, A. P., Muller-Nurasyid, M., Munroe, P. B., Nalls, M. A., Narisu, N., Nelson, C. P., Neville, M., Nielsen, S. F., Nikus, K., Njolstad, P. R., Nordestgaard, B. G., Nyholt, D. R., O'Connel, J. R., O'Donoghue, M. L., Loohuis, L. M. O., Ophoff, R. A., Owen, K. R., Packard, C. J., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pasterkamp, G., Patel, A. P., Pattie, A., Pedersen, O., Peissig, P. L., Peloso, G. M., Pennell, C. E., Perola, M., Perry, J. A., Perry, J. R. B., Pers, T. H., Person, T. N., Peters, A., Petersen, E. R. B., Peyser, P. A., Pirie, A., Polasek, O., Polderman, T. J., Puolijoki, H., Raitakari, O. T., Rasheed, A., Rauramaa, R., Reilly, D. F., Renstrom, F., Rheinberger, M., Ridker, P. M., Rioux, J. D., Rivas, M. A., Roberts, D. J., Robertson, N. R., Robino, A., Rolandsson, O., Rudan, I., Ruth, K. S., Saleheen, D., Salomaa, V., Samani, N. J., Sapkota, Y., Sattar, N., Schoen, R. E., Schreiner, P. J., Schulze, M. B., Scott, R. A., Segura-Lepe, M. P., Shah, S. H., Sheu, W. H. -H., Sim, X., Slater, A. J., Small, K. S., Smith, A. V., Southam, L., Spector, T. D., Speliotes, E. K., Starr, J. M., Stefansson, K., Steinthorsdottir, V., Stirrups, K. E., Strauch, K., Stringham, H. M., Stumvoll, M., Sun, L., Surendran, P., Swift, A. J., Tada, H., Tansey, K. E., Tardif, J. -C., Taylor, K. D., Teumer, A., Thompson, D. J., Thorleifsson, G., Thorsteinsdottir, U., Thuesen, B. H., Tonjes, A., Tromp, G., Trompet, S., Tsafantakis, E., Tuomilehto, J., Tybjaerg-Hansen, A., Tyrer, J. P., Uher, R., Uitterlinden, A. G., Uusitupa, M., Laan, S. W., Duijn, C. M., Leeuwen, N., van Setten, J., Vanhala, M., Varbo, A., Varga, T. V., Varma, R., Edwards, D. R. V., Vermeulen, S. H., Veronesi, G., Vestergaard, H., Vitart, V., Vogt, T. F., Volker, U., Vuckovic, D., Wagenknecht, L. E., Walker, M., Wallentin, L., Wang, F., Wang, C. A., Wang, S., Wang, Y., Ware, E. B., Wareham, N. J., Warren, H. R., Waterworth, D. M., Wessel, J., White, H. D., Willer, C. J., Wilson, J. G., Witte, D. R., Wood, A. R., Wu, Y., Yaghootkar, H., Yao, J., Yao, P., Yerges-Armstrong, L. M., Young, R., Zeggini, E., Zhan, X., Zhang, W., Zhao, J. H., Zhao, W., Zhou, W., Zondervan, K. T., Rotter, J. I., Pospisilik, J. A., Rivadeneira, F., Borecki, I. B., Deloukas, P., Frayling, T. M., Lettre, G., North, K. E., Lindgren, C. M., Hirschhorn, J. N., Loos, R. J. F., Turcot, V., Lu, Y., Highland, H. M., Schurmann, C., Justice, A. E., Fine, R. S., Bradfield, J. P., Esko, T., Giri, A., Graff, M., Guo, X., Hendricks, A. E., Karaderi, T., Lempradl, A., Locke, A. E., Mahajan, A., Marouli, E., Sivapalaratnam, S., Young, K. L., Alfred, T., Feitosa, M. F., Masca, N. G. D., Manning, A. K., Medina-Gomez, C., Mudgal, P., Ng, M. C. Y., Reiner, A. P., Vedantam, S., Willems, S. M., Winkler, T. W., Abecasis, G., Aben, K. K., Alam, D. S., Alharthi, S. E., Marchiori, Allison, Amouyel, P., Asselbergs, F. W., Auer, P. L., Balkau, B., Bang, L. E., Barroso, I., Bastarache, L., Benn, M., Bergmann, S., Bielak, L. F., Bluher, M., Boehnke, M., Boeing, H., Boerwinkle, E., Boger, C. A., Bork-Jensen, J., Bots, M. L., Bottinger, E. P., Bowden, D. W., Brandslund, I., Breen, G., Brilliant, M. H., Broer, L., Brumat, M., Burt, A. A., Butterworth, A. S., Campbell, P. T., Cappellani, S., Carey, D. J., Catamo, E., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Chowdhury, R., Christensen, C., Chu, A. Y., Cocca, M., Collins, F. S., Cook, J. P., Corley, J., Galbany, J. C., Cox, A. J., Crosslin, D. S., Cuellar-Partida, G., D'Eustacchio, A., Danesh, J., Davies, G., Bakker, P. I. W., Groot, M. C. H., Mutsert, R., Deary, I. J., Dedoussis, G., Demerath, E. W., Heijer, M., Hollander, A. I., Ruijter, H. M., Dennis, J. G., Denny, J. C., Di Angelantonio, E., Drenos, F., Du, M., Dube, M. -P., Dunning, A. M., Easton, D. F., Edwards, T. L., Ellinghaus, D., Ellinor, P. T., Elliott, P., Evangelou, E., Farmaki, A. -E., Farooqi, I. S., Faul, J. D., Fauser, S., Feng, S., Ferrannini, E., Ferrieres, J., Florez, J. C., Ford, I., Fornage, M., Franco, O. H., Franke, A., Franks, P. W., Friedrich, N., Frikke-Schmidt, R., Galesloot, T. E., Gan, W., Gandin, I., Gasparini, P., Gibson, J., Giedraitis, V., Gjesing, A. P., Gordon-Larsen, P., Gorski, M., Grabe, H. -J., Grant, S. F. A., Grarup, N., Griffiths, H. L., Grove, M. L., Gudnason, V., Gustafsson, S., Haessler, J., Hakonarson, H., Hammerschlag, A. R., Hansen, T., Harris, K. M., Harris, T. B., Hattersley, A. T., Have, C. T., Hayward, C., He, L., Heard-Costa, N. L., Heath, A. C., Heid, I. M., Helgeland, O., Hernesniemi, J., Hewitt, A. W., Holmen, O. L., Hovingh, G. K., Howson, J. M. M., Hu, Y., Huang, P. L., Huffman, J. E., Ikram, M. A., Ingelsson, E., Jackson, A. U., Jansson, J. -H., Jarvik, G. P., Jensen, G. B., Jia, Y., Johansson, S., Jorgensen, M. E., Jorgensen, T., Jukema, J. W., Kahali, B., Kahn, R. S., Kahonen, M., Kamstrup, P. R., Kanoni, S., Kaprio, J., Karaleftheri, M., Kardia, S. L. R., Karpe, F., Kathiresan, S., Kee, F., Kiemeney, L. A., Kim, E., Kitajima, H., Komulainen, P., Kooner, J. S., Kooperberg, C., Korhonen, T., Kovacs, P., Kuivaniemi, H., Kutalik, Z., Kuulasmaa, K., Kuusisto, J., Laakso, M., Lakka, T. A., Lamparter, D., Lange, E. M., Lange, L. A., Langenberg, C., Larson, E. B., Lee, N. R., Lehtimaki, T., Lewis, C. E., Li, H., Li, J., Li-Gao, R., Lin, H., Lin, K. -H., Lin, L. -A., Lin, X., Lind, L., Lindstrom, J., Linneberg, A., Liu, C. -T., Liu, D. J., Liu, Y., Lo, K. S., Lophatananon, A., Lotery, A. J., Loukola, A., Luan, J., Lubitz, S. A., Lyytikainen, L. -P., Mannisto, S., Marenne, G., Mazul, A. L., Mccarthy, M. I., McKean-Cowdin, R., Medland, S. E., Meidtner, K., Milani, L., Mistry, V., Mitchell, P., Mohlke, K. L., Moilanen, L., Moitry, M., Montgomery, G. W., Mook-Kanamori, D. O., Moore, C., Mori, T. A., Morris, A. D., Morris, A. P., Muller-Nurasyid, M., Munroe, P. B., Nalls, M. A., Narisu, N., Nelson, C. P., Neville, M., Nielsen, S. F., Nikus, K., Njolstad, P. R., Nordestgaard, B. G., Nyholt, D. R., O'Connel, J. R., O'Donoghue, M. L., Loohuis, L. M. O., Ophoff, R. A., Owen, K. R., Packard, C. J., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pasterkamp, G., Patel, A. P., Pattie, A., Pedersen, O., Peissig, P. L., Peloso, G. M., Pennell, C. E., Perola, M., Perry, J. A., Perry, J. R. B., Pers, T. H., Person, T. N., Peters, A., Petersen, E. R. B., Peyser, P. A., Pirie, A., Polasek, O., Polderman, T. J., Puolijoki, H., Raitakari, O. T., Rasheed, A., Rauramaa, R., Reilly, D. F., Renstrom, F., Rheinberger, M., Ridker, P. M., Rioux, J. D., Rivas, M. A., Roberts, D. J., Robertson, N. R., Robino, A., Rolandsson, O., Rudan, I., Ruth, K. S., Saleheen, D., Salomaa, V., Samani, N. J., Sapkota, Y., Sattar, N., Schoen, R. E., Schreiner, P. J., Schulze, M. B., Scott, R. A., Segura-Lepe, M. P., Shah, S. H., Sheu, W. H. -H., Sim, X., Slater, A. J., Small, K. S., Smith, A. V., Southam, L., Spector, T. D., Speliotes, E. K., Starr, J. M., Stefansson, K., Steinthorsdottir, V., Stirrups, K. E., Strauch, K., Stringham, H. M., Stumvoll, M., Sun, L., Surendran, P., Swift, A. J., Tada, H., Tansey, K. E., Tardif, J. -C., Taylor, K. D., Teumer, A., Thompson, D. J., Thorleifsson, G., Thorsteinsdottir, U., Thuesen, B. H., Tonjes, A., Tromp, G., Trompet, S., Tsafantakis, E., Tuomilehto, J., Tybjaerg-Hansen, A., Tyrer, J. P., Uher, R., Uitterlinden, A. G., Uusitupa, M., Laan, S. W., Duijn, C. M., Leeuwen, N., van Setten, J., Vanhala, M., Varbo, A., Varga, T. V., Varma, R., Edwards, D. R. V., Vermeulen, S. H., Veronesi, G., Vestergaard, H., Vitart, V., Vogt, T. F., Volker, U., Vuckovic, D., Wagenknecht, L. E., Walker, M., Wallentin, L., Wang, F., Wang, C. A., Wang, S., Wang, Y., Ware, E. B., Wareham, N. J., Warren, H. R., Waterworth, D. M., Wessel, J., White, H. D., Willer, C. J., Wilson, J. G., Witte, D. R., Wood, A. R., Wu, Y., Yaghootkar, H., Yao, J., Yao, P., Yerges-Armstrong, L. M., Young, R., Zeggini, E., Zhan, X., Zhang, W., Zhao, J. H., Zhao, W., Zhou, W., Zondervan, K. T., Rotter, J. I., Pospisilik, J. A., Rivadeneira, F., Borecki, I. B., Deloukas, P., Frayling, T. M., Lettre, G., North, K. E., Lindgren, C. M., Hirschhorn, J. N., and Loos, R. J. F.

Subjects
Publisher correction
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

18. Associations Between Attention-Deficit/Hyperactivity Disorder and Various Eating Disorders: A Swedish Nationwide Population Study Using Multiple Genetically Informative Approaches

Author

Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Yao, S., Kuja-Halkola, R., Martin, J., Lu, Y., Lichtenstein, P., Hubel, C., Almqvist, C., Magnusson, P. K., Bulik, C. M., Larsson, H., Norring, C., Birgegard, A., Yilmaz, Z., Watson, H., Baker, J., Thornton, L. M., Adan, R., Ando, T., Bergen, A., Berrettini, W., Boni, C., Boraska Perica, V., Brandt, H., Burghardt, R., Cassina, M., Cesta, C., Clementi, M., Coleman, J., Cone, R., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U., Davis, O., de Zwaan, M., Dedoussis, G., Degortes, D., Desocio, J., Dick, D., Dikeos, D., Dmitrzak-Weglarz, M., Docampo, E., Egberts, K., Ehrlich, S., Escaramis, G., Esko, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M., Finan, C., Fischer, K., Focker, M., Foretova, L., Forzan, M., Franklin, C., Gaspar, H., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K., Hatzikotoulas, K., Hauser, J., Hebebrand, J., Helder, S., Hendriks, J., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C., Hinney, A., Huckins, L., Hudson, J., Huemer, J., Imgart, H., Inoko, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Jureus, A., Kalsi, G., Kaminska, D., Kaplan, A., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M., Kaye, W., Kennedy, J., Kennedy, M., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Klump, K., Knudsen, G. P., Koeleman, B., Koubek, D., La Via, M., Landen, M., Levitan, R., Li, D., Lilenfeld, L., Lissowska, J., Magistretti, P., Maj, M., Mannik, K., Martin, N., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M., Nacmias, B., Nilsson, I., Ntalla, I., O'Toole, J., Pantel, J., Papezova, H., Parker, R., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Reichborn-Kjennerud, T., Ricca, V., Ripke, S., Ritschel, F., Roberts, M., Rotondo, A., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op't Landt, M., Slopien, A., Smith, T., Sorbi, S., Strengman, E., Strober, M., Sullivan, P., Szatkiewicz, J., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L., Tortorella, A., Tozzi, F., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A., van Furth, E., Wade, T., Wagner, G., Walton, E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Alfredsson, L., Andreassen, O., Aschauer, H., Barrett, J., Bencko, V., Carlberg, L., Cichon, S., Cohen-Woods, S., Dina, C., Ding, B., Espeseth, T., Floyd, J., Gallinger, S., Gambaro, G., Giegling, I., Herms, S., Janout, V., Julia, A., Klareskog, L., Le Hellard, S., Leboyer, M., Lundervold, A., Marsal, S., Mattingsdal, M., Navratilova, M., Ophoff, R., Palotie, A., Pinto, D., Ripatti, S., Rujescu, D., Scherer, S., Scott, L., Sladek, R., Soranzo, N., Southam, L., Steen, V., Wichmann, H. -E., Widen, E., Breen, G., Bulik, C., Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department Psychiatry [Chapel Hill], University of North Carolina System (UNC)-University of North Carolina System (UNC), Oregon Research Institute (ORI), Department of Psychiatry [Philadelphia], University of Pennsylvania [Philadelphia], Stockholm County Council, Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), University of Split, Azienda Ospedaliera di Padova, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Nutrition-Dietetics, Harokopio University of Athens, University of Athens Medical School [Athens], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Medstar Research Institute, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, National and Kapodistrian University of Athens (NKUA), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Weill Medical College of Cornell University [New York], Department of Genomics, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Icahn School of Medicine at Mount Sinai [New York] (MSSM), School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Tokai University, Institute for Marine and Antarctic Studies [Horbat] (IMAS), University of Tasmania [Hobart, Australia] (UTAS), National Institute for Health and Welfare [Helsinki], Medizinische Universität Wien = Medical University of Vienna, University of California [San Diego] (UC San Diego), University of California, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Computing [Dublin], Dublin City University [Dublin] (DCU), University of Helsinki, University Medical Center [Utrecht], Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Oak Ridge National Laboratory [Oak Ridge] (ORNL), UT-Battelle, LLC, The M Sklodowska-Curie Cancer Center and Institute of Oncology, Brain and Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Università degli studi della Campania 'Luigi Vanvitelli', Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Queensland Institute of Medical Research, MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Estonian Genome and Medicine, University of Tartu, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Institute of Psychiatry, King's College, Università degli Studi di Salerno (UNISA), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Vanderbilt University School of Medicine [Nashville], Charles University [Prague] (CU), Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K, Norwegian Institute of Public Health [Oslo] (NIPH), Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institute of Medical Informatics, Biometry and Epidemiology, The Scripps Translational Science Institute and The Scripps Research Institute, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Leiden University Medical Center (LUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, The Jackson Laboratory [Bar Harbor] (JAX), The Nofer Institute of Occupational Medicine, Università degli Studi di Perugia (UNIPG), Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Utrecht University [Utrecht], SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department Biostatistics University of North Carolina, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], Institute of Environmental Medicine, Karolinska Institutet [Stockholm]-Sachs' Children's Hospital, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Institute of Hygiene and Epidemiology, Charles University and General University Hospital-First Faculty of Medicine, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oslo (UiO), Familial Gastrointestinal Cancer Registry, Mount Sinai Hospital [Toronto, Canada] (MSH), Centre for Epidemiology and Biostatistics, Faculty of Medicine and Health Leeds, University of Leeds, Department of Optics [Univ Palacký], Faculty of Science [Univ Palacký], Palacky University Olomouc-Palacky University Olomouc, Vall d'Hebron University Hospital [Barcelona], Rheumatology Unit, University of Bergen (UiB), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Masaryk Memorial Cancer Institute (RECAMO), Department of Psychiatry, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Human Genetics [Montréal], McGill University = Université McGill [Montréal, Canada], Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Institute of Psychiatry-King‘s College London, Cardiff University-Medical Research Council, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
Adult, Male, Multifactorial Inheritance, Adolescent, behavioral disciplines and activities, Article, Feeding and Eating Disorders, Young Adult, [SCCO]Cognitive science, Polygenic risk score, Risk Factors, mental disorders, Humans, ADHD, Genetic epidemiology, Registries, Child, Sweden, [SDV.GEN]Life Sciences [q-bio]/Genetics, Eating disorder, Anorexia nervosa, Bulimia nervosa, Eating disorders, Attention Deficit Disorder with Hyperactivity, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; BACKGROUND:Although attention-deficit/hyperactivity disorder (ADHD) and eating disorders (EDs) frequently co-occur, little is known about the shared etiology. In this study, we comprehensively investigated the genetic association between ADHD and various EDs, including anorexia nervosa (AN) and other EDs such as bulimia nervosa.METHODS:We applied different genetically informative designs to register-based information of a Swedish nationwide population (N = 3,550,118). We first examined the familial coaggregation of clinically diagnosed ADHD and EDs across multiple types of relatives. We then applied quantitative genetic modeling in full-sisters and maternal half-sisters to estimate the genetic correlations between ADHD and EDs. We further tested the associations between ADHD polygenic risk scores and ED symptoms, and between AN polygenic risk scores and ADHD symptoms, in a genotyped population-based sample (N = 13,472).RESULTS:Increased risk of all types of EDs was found in individuals with ADHD (any ED: odds ratio [OR] = 3.97, 95% confidence interval [CI] = 3.81, 4.14; AN: OR = 2.68, 95% CI = 2.15, 2.86; other EDs: OR = 4.66, 95% CI = 4.47, 4.87; bulimia nervosa: OR = 5.01, 95% CI = 4.63, 5.41) and their relatives compared with individuals without ADHD and their relatives. The magnitude of the associations decreased as the degree of relatedness decreased, suggesting shared familial liability between ADHD and EDs. Quantitative genetic models revealed stronger genetic correlation of ADHD with other EDs (.37, 95% CI = .31, .42) than with AN (.14, 95% CI = .05, .22). ADHD polygenic risk scores correlated positively with ED symptom measures overall and with the subscales Drive for Thinness and Body Dissatisfaction despite small effect sizes.CONCLUSIONS:We observed stronger genetic association with ADHD for non-AN EDs than for AN, highlighting specific genetic correlation beyond a general genetic factor across psychiatric disorders.

Published
2019

19. An epigenome-wide view of osteoarthritis in target tissues

Author

Kreitmaier, P., primary, Suderman, M.J., additional, Southam, L., additional, Coutinho de Almeida, R., additional, Hatzikotoulas, K., additional, Meulenbelt, I., additional, Steinberg, J., additional, Relton, C.L., additional, Wilkinson, J.M., additional, and Zeggini, E., additional

Published
2021
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23. Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures (Nature Communications, (2019), 10, 1, (2054), 10.1038/s41467-019-09860-0)

Author

Styrkarsdottir, U, Stefansson, OA, Gunnarsdottir, K, Thorleifsson, G, Lund, SH, Stefansdottir, L, Juliusson, K, Agustsdottir, AB, Zink, F, Halldorsson, GH, Ivarsdottir, EV, Benonisdottir, S, Jonsson, H, Gylfason, A, Norland, K, Trajanoska, K, Boer, CG, Southam, L, Leung, JCS, Tang, NLS, Kwok, TCY, Lee, JSW, Ho, SC, Byrjalsen, I, Center, JR, Lee, SH, Koh, JM, Lohmander, LS, Ho-Pham, LT, Nguyen, TV, Eisman, JA, Woo, J, Leung, PC, Loughlin, J, Zeggini, E, Christiansen, C, Rivadeneira, F, van Meurs, J, Uitterlinden, AG, Mogensen, B, Ingvarsson, T, Sigurdsson, G, Benediktsson, R, Sulem, P, Jonsdottir, I, Masson, G, Holm, H, Norddahl, GL, Thorsteinsdottir, U, Gudbjartsson, DF, and Stefansson, K

Abstract

© 2019, The Author(s). The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file. In addition, affiliations 16 and 17 incorrectly read ‘School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia’ and ‘St Vincent’s Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.’ This has now been corrected in both the PDF and HTML versions of the Article.

Published
2019

24. Large-scale genome-wide meta-analyses provide insights for the development of new disease modifying targets for osteoarthritis

Author

Hatzikotoulas, K., primary, Boer, C., additional, Southam, L., additional, Stefánsdóttir, L., additional, Zhang, Y., additional, de Almeida, R., additional, Zheng, J., additional, Barysenka, A., additional, Meulenbelt, I., additional, Styrkársdóttir, U., additional, van Meurs, J., additional, Lee, M., additional, and Zeggini, E., additional

Published
2020
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28. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps (Nature Genetics, (2016), 48, 11, (1303-1312), 10.1038/ng.3668)

Author

Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., Soranzo, N., Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., and Soranzo, N.

Subjects
Author correction
Abstract

In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.

Published
2018

30. Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data

Author

Tachmazidou, I., Hatzikotoulas, K., Southam, L., Esparza-Gordillo, J., Haberland, V., Zheng, J., Johnson, T., Koprulu, M., Zengini, E., Steinberg, J., Wilkinson, J.M., Bhatnagar, S., Hoffman, J.D., Buchan, N., Süveges, D., Consortium, arcOGEN, Yerges-Armstrong, L., Smith, G.D., Gaunt, T.R., Scott, R.A., McCarthy, L.C., and Zeggini, E.

Abstract

Osteoarthritis is the most common musculoskeletal disease and the leading cause of disability globally. Here, we performed a genome-wide association study for osteoarthritis (77,052 cases and 378,169 controls), analyzing four phenotypes: knee osteoarthritis, hip osteoarthritis, knee and/or hip osteoarthritis, and any osteoarthritis. We discovered 64 signals, 52 of them novel, more than doubling the number of established disease loci. Six signals fine-mapped to a single variant. We identified putative effector genes by integrating expression quantitative trait loci (eQTL) colocalization, fine-mapping, and human rare-disease, animal-model, and osteoarthritis tissue expression data. We found enrichment for genes underlying monogenic forms of bone development diseases, and for the collagen formation and extracellular matrix organization biological pathways. Ten of the likely effector genes, including TGFB1 (transforming growth factor beta 1), FGF18 (fibroblast growth factor 18), CTSK (cathepsin K), and IL11 (interleukin 11), have therapeutics approved or in clinical trials, with mechanisms of action supportive of evaluation for efficacy in osteoarthritis.

Published
2019

31. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author

Haworth, S, Shapland, CY, Hayward, C, Prins, BP, Felix, JF, Medina-Gomez, C, Rivadeneira, F, Wang, C, Ahluwalia, TS, Vrijheid, M, Guxens, M, Sunyer, J, Tachmazidou, I, Walter, K, Iotchkova, V, Jackson, A, Cleal, L, Huffmann, J, Min, JL, Sass, L, Timmers, PRHJ, Al Turki, S, Anderson, CA, Anney, R, Antony, D, Artigas, MS, Ayub, M, Bala, S, Barrett, JC, Barroso, I, Beales, P, Bentham, J, Bhattacharya, S, Birney, E, Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G, Calissano, M, Carss, K, Charlton, R, Chatterjee, K, Chen, L, Ciampi, A, Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, DA, Cosgrove, C, Cox, T, Craddock, N, Crooks, L, Curran, S, Curtis, D, Daly, A, Danecek, P, Day, INM, Day-Williams, A, Dominiczak, A, Down, T, Du, Y, Dunham, I, Durbin, R, Edkins, S, Ekong, R, Ellis, P, Evans, DM, Farooqi, IS, Fitzpatrick, DR, Flicek, P, Floyd, J, Foley, AR, Franklin, CS, Futema, M, Gallagher, L, Gaunt, TR, Geihs, M, Geschwind, D, Greenwood, CMT, Griffin, H, Grozeva, D, Guo, X, Gurling, H, Hart, D, Hendricks, AE, Holmans, P, Howie, B, Huang, J, Huang, L, Hubbard, T, Humphries, SE, Hurles, ME, Hysi, P, Jackson, DK, Jamshidi, Y, Joyce, C, Karczewski, KJ, Kaye, J, Keane, T, Kemp, JP, Kennedy, K, Kent, A, Keogh, J, Khawaja, F, van Kogelenberg, M, Kolb-Kokocinski, A, Lachance, G, Langford, C, Lawson, D, Lee, I, Lek, M, Li, R, Li, Y, Liang, J, Lin, H, Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M, MacArthur, DG, Mangino, M, Marchini, J, Marenne, G, Maslen, J, Mathieson, I, McCarthy, S, McGuffin, P, McIntosh, AM, McKechanie, AG, McQuillin, A, Memari, Y, Metrustry, S, Migone, N, Mitchison, HM, Moayyeri, A, Morris, A, Morris, J, Muddyman, D, Muntoni, F, Northstone, K, O'Donovan, MC, O'Rahilly, S, Onoufriadis, A, Oualkacha, K, Owen, MJ, Palotie, A, Panoutsopoulou, K, Parker, V, Parr, JR, Paternoster, L, Paunio, T, Payne, F, Payne, SJ, Perry, JRB, Pietilainen, O, Plagnol, V, Pollitt, RC, Porteous, DJ, Povey, S, Quail, MA, Quaye, L, Raymond, FL, Rehnstrom, K, Richards, JB, Ridout, CK, Ring, S, Ritchie, GRS, Roberts, N, Robinson, RL, Savage, DB, Scambler, P, Schiffels, S, Schmidts, M, Schoenmakers, N, Scott, RH, Semple, RK, Serra, E, Sharp, SI, Shaw, A, Shihab, HA, Shin, S-Y, Skuse, D, Small, KS, Smee, C, Smith, BH, Soranzo, N, Southam, L, Spasic-Boskovic, O, Spector, TD, St Clair, D, Stalker, J, Stevens, E, Sun, J, Surdulescu, G, Suvisaari, J, Syrris, P, Taylor, R, Tian, J, Tobin, MD, Valdes, AM, Vandersteen, AM, Vijayarangakannan, P, Visscher, PM, Wain, LV, Walters, JTR, Wang, G, Wang, J, Wang, Y, Ward, K, Wheeler, E, Whyte, T, Williams, HJ, Williamson, KA, Wilson, C, Wilson, SG, Wong, K, Xu, C, Yang, J, Zhang, F, Zhang, P, Zheng, H-F, Smith, GD, Fisher, SE, Wilson, JF, Cole, TJ, Fernandez-Orth, D, Bonnelykke, K, Bisgaard, H, Pennell, CE, Jaddoe, VWV, Dedoussis, G, Timpson, N, Zeggini, E, Vitart, V, St Pourcain, B, UK10K Consortium, Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, and Child and Adolescent Psychiatry / Psychology

Abstract

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.

Published
2019

36. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author

Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), Pourcain, B.S. (Beate), Haworth, S., Shapland, C.Y., Hayward, C. (Caroline), Prins, B.P. (Bram), Felix, J.F. (Janine), Medina-Gomez, M.C. (Carolina), Rivadeneira Ramirez, F. (Fernando), Wang, C., Ahluwalia, TS, Vrijheid, M. (Martine), Guxens Junyent, M. (Mònica), Sunyer, J. (Jordi), Tachmazidou, I, Walter, K., Iotchkova, V, Jackson, A.U. (Anne), Cleal, L., Huffmann, J., Min, J. (Josine), Sass, L., Timmers, P, Al Turki, S., Anderson, CA, Anney, R. (Richard), Antony, D, Soler Artigas, M. (Maria), Ayub, M, Bala, S, Barrett, JC, Barroso, I.E. (Inês), Beales, P., Bentham, J, Bhattacharya, S. (Shoumo), Birney, E. (Ewan), Blackwood, D, Bobrow, M, Bochukova, E, Bolton, PF, Bounds, R, Boustred, C, Breen, G. (Gerome), Calissano, M, Carss, K, Charlton, R, Chatterjee, K. (Krishna), Chen, L. (Leslie), Ciampi, A. (Antonio), Cirak, S, Clapham, P, Clement, G, Coates, G, Cocca, M, Collier, D.A. (David), Cosgrove, C, Cox, T. (Tessa), Craddock, N.J. (Nick), Crooks, L, Curran, S, Curtis, D. (David), Daly, A, Danecek, P, Day, I.N.M. (Ian), Day-Williams, A, Dominiczak, A. (Anna), Down, T, Li, Y. (Yingrui), Dunham, D.M. (David), Durbin, R, Edkins, T. (Ted), Ekong, R. (Rosemary), Ellis, P. (Paul), Evans, D.M. (David), Farooqi, I.S. (Sadaf), Fitzpatrick, D.R. (David), Flicek, P, Floyd, J. (Jamie), Foley, AR, Franklin, C.S. (Christopher), Futema, M, Gallagher, L. (Louise), Gaunt, T.R. (Tom), Geihs, M, Geschwind, D., Greenwood, J.P. (John), Griffin, H, Grozeva, D. (Detelina), Guo, X.S., Guo, X. (Xiuqing), Gurling, H. (Hugh), Hart, D.J. (Deborah), Hendricks, AE, Holmans, P.A. (Peter), Howie, B, Huang, J. (Jian), Huang, L.R., Hubbard, T., Humphries, S.E. (Steve), Hurles, M.E. (Matthew), Hysi, P.G. (Pirro), Jackson, DK, Jamshidi, Y. (Yalda), Joyce, C, Karczewski, KJ, Kaye, J. (Jane), Keane, T, Kemp, J.P., Kennedy, K. (Karen), Kent, A. (Alistair), Keogh, J, Khawaja, F, van Kogelenberg, M., Kolb-Kokocinski, A, Lachance, G, Langford, C. (Cordelia), Lawson, D, Lee, I. van der, Lek, M, Li, R. (Rui), Li, Y.R. (Yun), Liang, J.Q., Lin, H., Liu, R, Lonnqvist, J, Lopes, LR, Lopes, M., MacArthur, DG, Mangino, M. (Massimo), Marchini, J. (Jonathan), Marenne, G., Maslen, J., Mathieson, I. (Iain), McCarthy, S. (Sean), Mcguffin, P. (Peter), Mcintosh, A.M. (Andrew), McKechanie, AG, McQuillin, A. (Andrew), Memari, Y, Metrustry, S. (Sarah), Migone, N, Mitchison, H.M. (Hannah), Moayyeri, A. (Alireza), Morris, A.D. (Andrew), Morris, J, Muddyman, D, Muntoni, F., Northstone, K. (Kate), O'Donovan, M. (Michael), O'Rahilly, S. (Stephen), Onoufriadis, A, Oualkacha, K., Owen, M.J., Palotie, A. (Aarno), Panoutsopoulou, K, Parker, V., Parr, D., Paternoster, L. (Lavinia), Paunio, T, Payne, F. (Felicity), Payne, SJ, Perry, J.B. (John), Pietiläinen, O.P.H. (Olli), Plagnol, V, Pollitt, RC, Porteous, D.J. (David J.), Povey, S. (Sue), Quail, MA, Quaye, L. (Lydia), Raymond, FL, Rehnström, K. (Karola), Richards, J.B. (Brent), Ridout, CK, Ring, S.M. (Susan), Ritchie, GRS, Roberts, N. (Nicola), Robinson, RL, Savage, D.B. (David), Scambler, P., Schiffels, S, Schmidts, M, Schoenmakers, N. (Nadia), Scott, RH, Semple, R.K. (Robert), Serra, E, Sharp, S.I., Shaw, A. (Alison), Shihab, HA, Shin, S.-Y., Skuse, D, Small, K.S. (Kerrin), Smee, C, Smith, B.H. (Blair), Soranzo, N. (Nicole), Southam, L. (Lorraine), Spasic-Boskovic, O, Spector, T.D. (Timothy), St. Clair, D. (David), Stalker, J, Stevens, E, Sun, J.P., Surdulescu, G, Suvisaari, J. (Jaana), Syrris, P, R. Taylor (Rohan), Tian, J., Tobin, M.D. (Martin), Valdes, A.M. (Ana Maria), Vandersteen, AM, Vijayarangakannan, P, Visscher, P.M. (Peter), Wain, L.V. (Louise), Walters, JTR, Wang, G. B., Wang, J. (Jinxia), Wang, Y. (Ying), Ward, K, Wheeler, E. (Eleanor), Whyte, T, Williams, HJ, Williamson, K.A., Wilson, C, Wilson, S.G. (Scott), Wong, K. (Kenny), Xu, CJ, Yang, J. (Jian), Zhang, F. (Feng), Zhang, P.B., Zheng, H.-F. (Hou-Feng), Smith, A.V. (Davey), Fisher, SE, Wilson, J.F. (James F), Cole, T.J. (T.), Fernandez-Orth, D., Bønnelykke, K. (Klaus), Bisgaard, H. (Hans), Pennell, C.E. (Craig), Jaddoe, V.W.V. (Vincent), Dedoussis, G, Timpson, N.J. (Nicholas), Zeggini, E. (Eleftheria), Vitart, V. (Veronique), and Pourcain, B.S. (Beate)

Abstract

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for lowfrequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carrie

Published
2019
Full Text
View/download PDF

37. GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

Author

Styrkarsdottir, U, Stefansson, O A, Gunnarsdottir, K, Thorleifsson, G, Lund, SH, Stefansdottir, L, Juliusson, K, Agustsdottir, AB, Zink, F, Halldorsson, GH, Ivarsdottir, EV, Benonisdottir, S, Jonsson, H, Gylfason, A, Norland, K, Trajanoska, Katerina, Boer, Cindy, Southam, L, Leung, JCS, Tang, NLS, Kwok, TCY, Lee, JSW, Ho, SC, Byrjalsen, I, Center, JR, Lee, SH, Koh, JM, Lohmander, LS, Ho-Pham, LT, Nguyen, TV, Eisman, JA, Woo, J, Leung, PC, Loughlin, J, Zeggini, E, Christiansen, C, Rivadeneira, Fernando, van Meurs, Joyce, Uitterlinden, André, Mogensen, B, Ingvarsson, T, Sigurdsson, G, Benediktsson, R, Sulem, P, Jonsdottir, I, Masson, G, Holm, H, Norddahl, GL, Thorsteinsdottir, U, Gudbjartsson, DF, Stefansson, K, Styrkarsdottir, U, Stefansson, O A, Gunnarsdottir, K, Thorleifsson, G, Lund, SH, Stefansdottir, L, Juliusson, K, Agustsdottir, AB, Zink, F, Halldorsson, GH, Ivarsdottir, EV, Benonisdottir, S, Jonsson, H, Gylfason, A, Norland, K, Trajanoska, Katerina, Boer, Cindy, Southam, L, Leung, JCS, Tang, NLS, Kwok, TCY, Lee, JSW, Ho, SC, Byrjalsen, I, Center, JR, Lee, SH, Koh, JM, Lohmander, LS, Ho-Pham, LT, Nguyen, TV, Eisman, JA, Woo, J, Leung, PC, Loughlin, J, Zeggini, E, Christiansen, C, Rivadeneira, Fernando, van Meurs, Joyce, Uitterlinden, André, Mogensen, B, Ingvarsson, T, Sigurdsson, G, Benediktsson, R, Sulem, P, Jonsdottir, I, Masson, G, Holm, H, Norddahl, GL, Thorsteinsdottir, U, Gudbjartsson, DF, and Stefansson, K

Published
2019

40. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L. M., Hatzikotoulas, K., Curtis, C., Esko, T., Espeseth, T., Estivill, X., Favaro, A., Fernández-Aranda, F., Fichter, M. M., Finan, C., Fischer, K., Floyd, J. A. B., Foretova, L., Rhodes, D., Forzan, M., Franklin, C. S., Gallinger, S., Gambaro, G., Gaspar, H. A., Giegling, I., Gonidakis, F., Gorwood, P., Gratacos, M., Guillaume, S., Moens, J., Guo, Y., Hakonarson, H., Halmi, K. A., Hauser, J., Hebebrand, J., Helder, S., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Kalsi, G., Hilliard, C. E., Hinney, A., Hübel, C., Hudson, J. I., Huemer, J., Inoko, H., Janout, V., Jiménez-Murcia, S., Johnson, C., Dempster, D., Julià, A., Juréus, A., Kaminska, D., Kaplan, A. S., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W., Leung, R., Kennedy, J. L., Keski-Rahkonen, A., Kiezebrink, K., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Koeleman, B. P. C., Koubek, D., La Via, M. C., Landén, M., Keohane, A., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Lilenfeld, L., Lissowska, J., Lundervold, A., Magistretti, P., Maj, M., Mannik, K., Burghardt, R., Marsal, S., Martin, N., Mattingsdal, M., McDevitt, S., McGuffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Ehrlich, S., Mitchell, K., Monteleone, P., Monteleone, A. M., Mortensen, P., Munn-Chernoff, M. A., Navratilova, M., Nilsson, I., Norring, C., Ntalla, I., Ophoff, R. A., O'Toole, J. K., Palotie, A., Pante, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Southam, L., Reichborn-Kjennerud, T., Ripatti, S., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schmidt, U., Ludolph, A., Schork, N. J., Schosser, A., Slachtova, L., Sladek, R., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Soranzo, N., Steen, V. M., Walton, E., Strengman, E., Strober, M., Sullivan, P. F., Szatkiewicz, J. P., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Thornton, L. M., Tortorella, A., Tozzi, F., Deloukas, P., Treasure, J., Tsitsika, A., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wagner, G., Watson, H., Wichmann, H-E, Widen, E., Hofman, A., Woodside, D. B., Yanovski, J., Yao, S., Yilmaz, Z., Zeggini, E., Zerwas, S., Zipfel, S., Palta, P., van Rooij, F. J. A., Stirrups, K., Adan, R., Boni, C., Cone, R., Dedoussis, G., van Furth, E., Hudson, J., Kas, M., Keski-Rahonen, A., Steinberg, J., Knudsen, G-P, Raevuori, A. H., Aguilera-McKay, F., van Elburg, A., Consortium, Eating Disorder Working Group of the Psychiatric Genomics, Collier, D. A., Breen, G., Bulik, C. M., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Aschauer, H., Baker, J. H., Barrett, J. C., Bencko, V., Bergen, A. W., Berrettini, W. H., Birgegard, A., Boraska Perica, V., Brandt, H., Carlberg, L., Cassina, M., Cichon, S., Clementi, M., Cohen-Woods, S., Coleman, J., Cone, R. D., Gunasinghe, C., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U. N., Davis, O. S. P., de Zwaan, M., Degortes, D., DeSocio, J. E., Romero, A., Dick, D. M., Dikeos, D., Dina, C., Ding, B., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L., Egberts, K., Escaramís, G., Inconnu, Institut Pasteur de Côte d'Ivoire, Réseau International des Instituts Pasteur (RIIP), Laboratoire de bactériologie-virologie, CHU de Yopougon, Department of Nutrition Science & Dietetics, Harokopio University, Analyse Phenotypique, Developpementale et Genetique des Comportements Addictifs, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Clinicum, University of Helsinki, Department of Public Health, Anna Keski-Rahkonen / Principal Investigator, HUS Children and Adolescents, Genomics of Neurological and Neuropsychiatric Disorders, Genetic Epidemiology, Eating Disorder Working Group of the Psychiatric Genomics Consortium, Epidemiology, Kas lab, Huckins, L. M., Hatzikotoulas, K., Southam, L., Thornton, L. M., Steinberg, J., Aguilera-Mckay, F., Treasure, J., Schmidt, U., Gunasinghe, C., Romero, A., Curtis, C., Rhodes, D., Moens, J., Kalsi, G., Dempster, D., Leung, R., Keohane, A., Burghardt, R., Ehrlich, S., Hebebrand, J., Hinney, A., Ludolph, A., Walton, E., Deloukas, P., Hofman, A., Palotie, A., Palta, P., van Rooij, F. J. A., Stirrups, K., Adan, R., Boni, C., Cone, R., Dedoussis, G., van Furth, E., Gonidakis, F., Gorwood, P., Hudson, J., Kaprio, J., Kas, M., Keski-Rahonen, A., Kiezebrink, K., Knudsen, G. -P., Slof-Op 'T Landt, M. C. T., Maj, M., Monteleone, A. M., Monteleone, P., Raevuori, A. H., Reichborn-Kjennerud, T., Tozzi, F., Tsitsika, A., Elburg, A., Collier, D. A., Sullivan, P. F., Breen, G., Bulik, C. M., Zeggini, E., Adan, R. A. H., Alfredsson, L., Ando, T., Andreassen, O. A., Aschauer, H., Baker, J. H., Barrett, J. C., Bencko, V., Bergen, A. W., Berrettini, W. H., Birgegard, A., Perica, V. B., Brandt, H., Carlberg, L., Cassina, M., Cichon, S., Clementi, M., Cohen-Woods, S., Coleman, J., Cone, R. D., Courtet, P., Crawford, S., Crow, S., Crowley, J., Danner, U. N., Davis, O. S. P., Zwaan, M., Degortes, D., Desocio, J. E., Dick, D. M., Dikeos, D., Dina, C., Ding, B., Dmitrzak-Weglarz, M., Docampo, E., Duncan, L., Egberts, K., Escaramis, G., Esko, T., Espeseth, T., Estivill, X., Favaro, A., Fernandez-Aranda, F., Fichter, M. M., Finan, C., Fischer, K., Floyd, J. A. B., Foretova, L., Forzan, M., Franklin, C. S., Gallinger, S., Gambaro, G., Gaspar, H. A., Giegling, I., Gratacos, M., Guillaume, S., Guo, Y., Hakonarson, H., Halmi, K. A., Hauser, J., Helder, S., Herms, S., Herpertz-Dahlmann, B., Herzog, W., Hilliard, C. E., Hubel, C., Hudson, J. I., Huemer, J., Inoko, H., Janout, V., Jimenez-Murcia, S., Johnson, C., Julia, A., Jureus, A., Kaminska, D., Kaplan, A. S., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W., Kennedy, J. L., Keski-Rahkonen, A., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Koeleman, B. P. C., Koubek, D., Via, M. C. L., Landen, M., Hellard, S. L., Levitan, R. D., Li, D., Lichtenstein, P., Lilenfeld, L., Lissowska, J., Lundervold, A., Magistretti, P., Mannik, K., Marsal, S., Martin, N., Mattingsdal, M., Mcdevitt, S., Mcguffin, P., Merl, E., Metspalu, A., Meulenbelt, I., Micali, N., Mitchell, J., Mitchell, K., Mortensen, P., Munn-Chernoff, M. A., Navratilova, M., Nilsson, I., Norring, C., Ntalla, I., Ophoff, R. A., O'Toole, J. K., Pantel, J., Papezova, H., Pinto, D., Rabionet, R., Raevuori, A., Rajewski, A., Ramoz, N., Rayner, N. W., Ripatti, S., Roberts, M., Rotondo, A., Rujescu, D., Rybakowski, F., Santonastaso, P., Scherag, A., Scherer, S. W., Schork, N. J., Schosser, A., Slachtova, L., Sladek, R., Slagboom, P. E., Slopien, A., Soranzo, N., Steen, V. M., Strengman, E., Strober, M., Szatkiewicz, J. P., Szeszenia-Dabrowska, N., Tachmazidou, I., Tenconi, E., Tortorella, A., Tziouvas, K., Elburg, A. A., Furth, E. F., Wagner, G., Watson, H., Wichmann, H. -E., Widen, E., Woodside, D. B., Yanovski, J., Yao, S., Yilmaz, Z., Zerwas, S., and Zipfel, S.

Subjects
Male, 0301 basic medicine, Anorexia Nervosa, [SDV]Life Sciences [q-bio], Intron, Medizin, Genome-wide association study, Genome, 3124 Neurology and psychiatry, Intergenic region, Molecular Biology, Psychiatry and Mental Health, Cellular and Molecular Neuroscience, Exome, HYPOGONADOTROPIC HYPOGONADISM, GENE-EXPRESSION, Genetics, Bulimia nervosa, ASSOCIATION, GPI-Linked Protein, 3. Good health, CONTROLLED-TRIALS, Psychiatry and Mental health, Eating disorders, Phenotype, CONTROLLED FAMILY, Female, Original Article, Human, Genotype, In silico, European Continental Ancestry Group, Locus (genetics), Biology, GPI-Linked Proteins, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, BULIMIA-NERVOSA, medicine, Journal Article, Humans, Family, Genetic Predisposition to Disease, ddc:610, Genetic association, AUTISM SPECTRUM DISORDER, 3112 Neurosciences, Genetic Variation, Correction, EATING-DISORDERS, ARACHIDONIC-ACID, medicine.disease, Introns, 030104 developmental biology, Cell Adhesion Molecule, RISK-FACTORS, 3111 Biomedicine, Cell Adhesion Molecules, Genome-Wide Association Study
Abstract

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10−6), and rs7700147, an intergenic variant (P=2.93 × 10−5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Published
2017

41. Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis

Author

Steinberg, J., Brooks, R.A., Southam, L., Bhatnagar, S., Roumeliotis, T.I., Hatzikotoulas, K., Zengini, E., Wilkinson, J.M., Choudhary, J.S., McCaskie, A.W., and Zeggini, E.

Abstract

Objectives: To identify molecular differences between chondrocytes from osteophytic and articular cartilage tissue from OA patients. Methods: We investigated genes and pathways by combining genome-wide DNA methylation, RNA sequencing and quantitative proteomics in isolated primary chondrocytes from the cartilaginous layer of osteophytes and matched areas of low- and high-grade articular cartilage across nine patients with OA undergoing hip replacement surgery. Results: Chondrocytes from osteophytic cartilage showed widespread differences to low-grade articular cartilage chondrocytes. These differences were similar to, but more pronounced than, differences between chondrocytes from osteophytic and high-grade articular cartilage, and more pronounced than differences between high- and low-grade articular cartilage. We identified 56 genes with significant differences between osteophytic chondrocytes and low-grade articular cartilage chondrocytes on all three omics levels. Several of these genes have known roles in OA, including ALDH1A2 and cartilage oligomeric matrix protein, which have functional genetic variants associated with OA from genome-wide association studies. An integrative gene ontology enrichment analysis showed that differences between osteophytic and low-grade articular cartilage chondrocytes are associated with extracellular matrix organization, skeletal system development, platelet aggregation and regulation of ERK1 and ERK2 cascade. Conclusion: We present a first comprehensive view of the molecular landscape of chondrocytes from osteophytic cartilage as compared with articular cartilage chondrocytes from the same joints in OA. We found robust changes at genes relevant to chondrocyte function, providing insight into biological processes involved in osteophyte development and thus OA progression.

Published
2018

42. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)

Author

Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Di Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Consortium, GG, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences

Published
2018

43. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)

Author

Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences

Published
2018

44. Combination therapy as a potential risk factor for the development of type 2 diabetes in patients with schizophrenia: The GOMAP study

Author

Mamakou, V. Hackinger, S. Zengini, E. Tsompanaki, E. Marouli, E. Serafetinidis, I. Prins, B. Karabela, A. Glezou, E. Southam, L. Rayner, N.W. Kuchenbaecker, K. Lamnissou, K. Kontaxakis, V. Dedoussis, G. Gonidakis, F. Thanopoulou, A. Tentolouris, N. Zeggini, E.

Subjects
nutritional and metabolic diseases
Abstract

Background: Schizophrenia (SCZ) is associated with increased risk of type 2 diabetes (T2D). The potential diabetogenic effect of concomitant application of psychotropic treatment classes in patients with SCZ has not yet been evaluated. The overarching goal of the Genetic Overlap between Metabolic and Psychiatric disease (GOMAP) study is to assess the effect of pharmacological, anthropometric, lifestyle and clinical measurements, helping elucidate the mechanisms underlying the aetiology of T2D. Methods: The GOMAP case-control study (Genetic Overlap between Metabolic and Psychiatric disease) includes hospitalized patients with SCZ, some of whom have T2D. We enrolled 1653 patients with SCZ; 611 with T2D and 1042 patients without T2D. This is the first study of SCZ and T2D comorbidity at this scale in the Greek population. We retrieved detailed information on first- and second-generation antipsychotics (FGA, SGA), antidepressants and mood stabilizers, applied as monotherapy, 2-drug combination, or as 3- or more drug combination. We assessed the effects of psychotropic medication, body mass index, duration of schizophrenia, number of hospitalizations and physical activity on risk of T2D. Using logistic regression, we calculated crude and adjusted odds ratios (OR) to identify associations between demographic factors and the psychiatric medications. Results: Patients with SCZ on a combination of at least three different classes of psychiatric drugs had a higher risk of T2D [OR 1.81 (95% CI 1.22-2.69); p=0.003] compared to FGA alone therapy, after adjustment for age, BMI, sex, duration of SCZ and number of hospitalizations. We did not find evidence for an association of SGA use or the combination of drugs belonging to two different classes of psychiatric medications with increased risk of T2D [1.27 (0.84-1.93), p=0.259 and 0.98 (0.71-1.35), p=0.885, respectively] compared to FGA use. Conclusions: We find an increased risk of T2D in patients with SCZ who take a combination of at least three different psychotropic medication classes compared to patients whose medication consists only of one or two classes of drugs. © 2018 The Author(s).

Published
2018

45. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, Laura M., Hatzikotoulas, Konstantinos, Southam, L., Thornton, Laura M., Steinberg, J.S., Aguilera-McKay, F, Treasure, J., Schmidt, U., Gunasinghe, C, Romero, Atocha, Curtis, Charles, Rhodes, Davina H., Bernelot Moens, Hein J, Kalsi, Gursharan, Dempster, D, Leung, R, Keohane, A, Burghardt, Roland, Ehrlich, S., Hebebrand, J., Hinney, A., Ludolph, A., Walton, Esther, Deloukas, P., Hofman, A., Palotie, A., Palta, P., Van Rooij, Frank J A, Stirrups, Kathleen, Adan, R, Boni, Claudette, Cone, Roger, Dedoussis, George, Furth, E.E., Gonidakis, Fragiskos, Gorwood, P., Hudson, Thomas J., Kaprio, Jaakko, Kas, M, Keski-Rahonen, A, Kiezebrink, K., Knudsen, Gun Peggy S., Slof-Op 't Landt, M C T, Maj, Mario, Monteleone, Alessio Maria, Monteleone, Palmiero, Raevuori, A H, Reichborn-Kjennerud, Ted, Tozzi, F., Tsitsika, Artemis, and Eating Disorder Working Group of the Psychiatric Genomics Consortium

Abstract

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10-6), and rs7700147, an intergenic variant (P=2.93 × 10-5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.Molecular Psychiatry advance online publication, 25 July 2017; doi:10.1038/mp.2017.88.

Published
2018

46. Correction to: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa (Molecular Psychiatry, (2018), 23, 5, (1169-1180), 10.1038/mp.2017.88)

Author

Huckins, L.M. Hatzikotoulas, K. Southam, L. Thornton, L.M. Steinberg, J. Aguilera-McKay, F. Treasure, J. Schmidt, U. Gunasinghe, C. Romero, A. Curtis, C. Rhodes, D. Moens, J. Kalsi, G. Dempster, D. Leung, R. Keohane, A. Burghardt, R. Ehrlich, S. Hebebrand, J. Hinney, A. Ludolph, A. Walton, E. Deloukas, P. Hofman, A. Palotie, A. Palta, P. van Rooij, F.J.A. Stirrups, K. Adan, R. Boni, C. Cone, R. Dedoussis, G. van Furth, E. Gonidakis, F. Gorwood, P. Hudson, J. Kaprio, J. Kas, M. Keski-Rahonen, A. Kiezebrink, K. Knudsen, G.-P. Maj, M. Monteleone, A.M. Monteleone, P. Raevuori, A.H. Reichborn-Kjennerud, T. Tozzi, F. Tsitsika, A. van Elburg, A. Collier, D.A. Sullivan, P.F. Breen, G. Bulik, C.M. Zeggini, E. MCT Slof-Op 't Landt Eating Disorder Working Group of the Psychiatric Genomics Consortium

Subjects
GeneralLiterature_INTRODUCTORYANDSURVEY
Abstract

The fortieth author’s name was listed incorrectly. The correct presentation is A Keski-Rahkonen. © 2018, Springer Nature Limited.

Published
2018

47. Genome-wide analyses using UK biobank data povide new therapeutic targets for osteoarthritis

Author

Hatzikotoulas, K., primary, Tachmazidou, I., additional, Southam, L., additional, Esparza-Gordillo, J., additional, Haberland, V., additional, Zheng, J., additional, Johnson, T., additional, Koprulu, M., additional, Zengini, E., additional, Steinberg, J., additional, Wilkinson, J., additional, Bhatnagar, S., additional, Hoffman, J., additional, Buchan, N., additional, Süveges, D., additional, Yerges-Armstrong, L., additional, Davey-Smith, G., additional, Gaunt, T., additional, Scott, R., additional, McCarthy, L., additional, and Zeggini, E., additional

Published
2019
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48. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author

Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), and Soranzo, N. (Nicole)

Abstract

In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.

Published
2018
Full Text
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49. Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-McKay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (A.), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (Panagiotis), Hofman, A. (Albert), Palotie, A. (Aarno), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R.A.H. (Roger), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G-P), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (Artemis), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), Zeggini, E. (E.), Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-McKay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (A.), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (Panagiotis), Hofman, A. (Albert), Palotie, A. (Aarno), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R.A.H. (Roger), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G-P), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (Artemis), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), and Zeggini, E. (E.)

Abstract

The fortieth author's name was listed incorrectly. The correct presentation is A Keski-Rahkonen.

Published
2018
Full Text
View/download PDF

50. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa

Author

Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-Mckay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (Atocha), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (P.), Hofman, A. (A.), Palotie, A. (A.), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R. (R.), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G. P.), Slof-Op 'T Landt, M.C.T. (M. C.T.), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (A.), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), Zeggini, E. (E.), Huckins, L.M. (L. M.), Hatzikotoulas, K. (K.), Southam, L. (Lorraine), Thornton, L.M. (L. M.), Steinberg, J. (J.), Aguilera-Mckay, F. (F.), Treasure, J. (J.), Schmidt, U. (U.), Gunasinghe, C. (C.), Romero, A. (Atocha), Curtis, C. (C.), Rhodes, D. (D.), Moens, J. (J.), Kalsi, G. (G.), Dempster, D. (D.), Leung, R. (R.), Keohane, A. (A.), Burghardt, R. (R.), Ehrlich, S.M. (Stefan), Hebebrand, J. (Johannes), Hinney, A. (Anke), Ludolph, A.C. (Albert), Walton, E. (Esther), Deloukas, P. (P.), Hofman, A. (A.), Palotie, A. (A.), Palta, P. (Priit), Rooij, F.J.A. (Frank) van, Stirrups, K. (Kathy), Adan, R. (R.), Boni, C. (C.), Cone, R. (R.), Dedoussis, G.V. (George), Furth, E.F. (Eric) van, Gonidakis, F. (F.), Gorwood, P. (P.), Hudson, J. (J.), Kaprio, J. (J.), Kas, M.J.H. (Martien), Keski-Rahonen, A. (A.), Kiezebrink, K. (K.), Knudsen, G.-P. (G. P.), Slof-Op 'T Landt, M.C.T. (M. C.T.), Maj, M. (M.), Monteleone, A.M. (Alessio Maria), Monteleone, P. (P.), Raevuori, A.H. (A. H.), Reichborn-Kjennerud, T. (T.), Tozzi, F. (F.), Tsitsika, A. (A.), Elburg, A.A. (Annemarie) van, Collier, D.A. (David), Sullivan, P.F. (Patrick), Breen, G. (Gerome), Bulik, C.M. (C. M.), and Zeggini, E. (E.)

Abstract

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10 -6), and rs7700147, an intergenic variant (P=2.93 × 10 -5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Published
2018
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