Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

被引：484

作者：

Berndt, Sonja I. ^{[1
]}

Gustafsson, Stefan ^{[2
,3
]}

Maegi, Reedik ^{[4
,5
]}

Ganna, Andrea ^{[3
]}

Wheeler, Eleanor ^{[6
]}

Feitosa, Mary F. ^{[7
]}

Justice, Anne E. ^{[8
]}

Monda, Keri L. ^{[8
,9
]}

Croteau-Chonka, Damien C. ^{[10
]}

Day, Felix R. ^{[11
]}

Esko, Tonu ^{[5
,12
]}

Fall, Tove ^{[3
]}

Ferreira, Teresa ^{[4
]}

Gentilini, Davide ^{[13
]}

Jackson, Anne U. ^{[14
]}

Luan, Jian'an ^{[11
]}

Randall, Joshua C. ^{[4
,6
]}

Vedantam, Sailaja ^{[15
,16
,17
,18
,19
]}

Willer, Cristen J. ^{[20
,21
,22
]}

Winkler, Thomas W. ^{[23
]}

Wood, Andrew R. ^{[24
]}

Workalemahu, Tsegaselassie ^{[25
,26
,27
]}

Hu, Yi-Juan

Lee, Sang Hong ^{[28
]}

Liang, Liming ^{[29
,30
]}

Lin, Dan-Yu ^{[31
]}

Min, Josine L. ^{[4
]}

Neale, Benjamin M. ^{[32
]}

Thorleifsson, Gudmar ^{[33
]}

Yang, Jian ^{[34
,35
]}

Albrecht, Eva ^{[36
]}

Amin, Najaf ^{[36
]}

Bragg-Gresham, Jennifer L. ^{[14
]}

Cadby, Gemma ^{[38
,39
,40
]}

den Heijer, Martin ^{[41
]}

Eklund, Niina ^{[42
]}

Fischer, Krista ^{[5
]}

Goel, Anuj ^{[43
]}

Hottenga, Jouke-Jan ^{[44
]}

Huffman, Jennifer E. ^{[45
]}

Jarick, Ivonne ^{[46
]}

Johansson, Asa ^{[47
,48
]}

Johnson, Toby ^{[49
,50
]}

Kanoni, Stavroula ^{[6
]}

Kleber, Marcus E. ^{[51
]}

Koenig, Inke R. ^{[52
,53
]}

Kristiansson, Kati ^{[42
]}

Kutalik, Zoltn ^{[54
,55
]}

Lamina, Claudia ^{[56
]}

Lecoeur, Cecile ^{[57
,58
]}

机构：

[1] NCI, US Dept HHS, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA

[2] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden

[3] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[5] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[6] Wellcome Trust Sanger Inst, Cambridge, England

[7] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[8] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA

[9] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA USA

[10] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[11] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England

[12] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia

[13] Ist Auxol Italiano, Dept Mol Biol, Milan, Italy

[14] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[15] Childrens Hosp, Div Genet, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA

[16] Childrens Hosp, Div Endocrinol, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA

[17] Broad Inst, Metab Initiat, Cambridge, MA USA

[18] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA

[19] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[20] Univ Michigan, Dept Internal Med Cardiovasc, Ann Arbor, MI 48109 USA

[21] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA

[22] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[23] Univ Regensburg, Med Ctr, Inst Epidemiol & Prevent Med, D-93053 Regensburg, Germany

[24] Univ Exeter, Peninsula Coll Med & Dent, Exeter, Devon, England

[25] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[26] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA

[27] Harvard Univ, Sch Med, Boston, MA USA

[28] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA

[29] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[30] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[31] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA

[32] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[33] deCODE Genet, Reykjavik, Iceland

[34] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia

[35] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[36] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany

[37] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[38] Ontario Inst Canc Res, Toronto, ON, Canada

[39] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada

[40] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Crawley, WA, Australia

[41] Vrije Univ Amsterdam, Med Ctr, Dept Internal Med, Amsterdam, Netherlands

[42] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Gen, Helsinki, Finland

[43] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[44] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[45] Western Gen Hosp, MRC, Inst Genet & Mol Med, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[46] Univ Marburg, Inst Med Biometry & Epidemiol, Marburg, Germany

[47] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden

[48] Univ Uppsala Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden

[49] Queen Mary Univ London, Barts & London Sch Med & Dent, Genome Ctr, London, England

[50] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England

来源：

NATURE GENETICS | 2013年 / 45卷 / 05期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院; 瑞典研究理事会; 欧洲研究理事会; 澳大利亚研究理事会; 瑞士国家科学基金会;

关键词：

BODY-MASS INDEX; MISSING HERITABILITY; COMMON VARIANTS; EXTREME OBESITY; CONFER RISK; EARLY-ONSET; ASSOCIATION; POPULATION; EXPRESSION; SORTILIN;

D O I：

10.1038/ng.2606

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

引用

页码：501 / U69

页数：14

共 50 条

[31] International genome-wide association study meta-analysis identifies 49 new psoriasis-associated genetic loci
Dand, N.
BRITISH JOURNAL OF DERMATOLOGY, 2022, 186 (01) : E3 - E3
[32] Genome-wide meta-analysis identifies 3 novel loci associated with stroke
Malik, Rainer
Rannikmaee, Kristiina
Traylor, Matthew
Georgakis, Marios K.
Sargurupremraj, Muralidharan
Markus, Hugh S.
Hopewell, Jemma C.
Debette, Stephanie
Sudlow, Cathie L. M.
Dichgans, Martin
ANNALS OF NEUROLOGY, 2018, 84 (06) : 934 - 939
[33] Genome-Wide Meta-Analysis Identifies Two Novel Risk Loci for Epilepsy
Song, Meng
Liu, Jiewei
Yang, Yongfeng
Lv, Luxian
Li, Wenqiang
Luo, Xiong-Jian
FRONTIERS IN NEUROSCIENCE, 2021, 15
[34] Genome-wide association meta-analysis identifies six loci for osteocalcin levels
Hsu, Yi-Hsiang
Karasik, David
Kiel, Douglas P.
Teumer, Alexander
Trajanoska, Katerina
Rivadeneira, Fernando
JOURNAL OF BONE AND MINERAL RESEARCH, 2019, 34 : 78 - 79
[35] GENOME-WIDE ASSOCIATION META-ANALYSIS IDENTIFIES NOVEL LOCI FOR KIDNEY FAILURE
van der Most, Peter
Wang, Siqi
Guan, Weihua
Schladt, David
Loza, Bao-Li
Stapleton, Caragh
Heinzel, Andreas
Israni, Ajay
Jacobson, Pamala
Keating, Brendan
Conlon, Peter
Oberbauer, Rainer
Snieder, Harold
De Borst, Martin
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2022, 37 : I800 - I801
[36] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci
Patsopoulos, Nikolaos A.
de Bakker, Paul I. W.
ANNALS OF NEUROLOGY, 2011, 70 (06) : 897 - 912
[37] Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis
van Rooij, Frank J. A.
Qayyum, Rehan
Smith, Albert V.
Zhou, Yi
Trompet, Stella
Tanaka, Toshiko
Keller, Margaux F.
Chang, Li-Ching
Schmidt, Helena
Yang, Min-Lee
Chen, Ming-Huei
Hayes, James
Johnson, Andrew D.
Yanek, Lisa R.
Mueller, Christian
Lange, Leslie
Floyd, James S.
Ghanbari, Mohsen
Zonderman, Alan B.
Jukema, J. Wouter
Hofman, Albert
van Duijn, Cornelia M.
Desch, Karl C.
Saba, Yasaman
Ozel, Ayse B.
Snively, Beverly M.
Wu, Jer-Yuarn
Schmidt, Reinhold
Fornage, Myriam
Klein, Robert J.
Fox, Caroline S.
Matsuda, Koichi
Kamatani, Naoyuki
Wild, Philipp S.
Stott, David J.
Ford, Ian
Slagboom, P. Eline
Yang, Jaden
Chu, Audrey Y.
Lambert, Amy J.
Uitterlinden, Andre G.
Franco, Oscar H.
Hofer, Edith
Ginsburg, David
Hu, Bella
Keating, Brendan
Schick, Ursula M.
Brody, Jennifer A.
Li, Jun Z.
Chen, Zhao
AMERICAN JOURNAL OF HUMAN GENETICS, 2017, 100 (01) : 51 - 63
[38] Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Chia, Ruth
Sabir, Marya S.
Bandres-Ciga, Sara
Saez-Atienzar, Sara
Reynolds, Regina H.
Gustavsson, Emil
Walton, Ronald L.
Ahmed, Sarah
Viollet, Coralie
Ding, Jinhui
Makarious, Mary B.
Diez-Fairen, Monica
Portley, Makayla K.
Shah, Zalak
Abramzon, Yevgeniya
Hernandez, Dena G.
Blauwendraat, Cornelis
Stone, David J.
Eicher, John
Parkkinen, Laura
Ansorge, Olaf
Clark, Lorraine
Honig, Lawrence S.
Marder, Karen
Lemstra, Afina
St George-Hyslop, Peter
Londos, Elisabet
Morgan, Kevin
Lashley, Tammaryn
Warner, Thomas T.
Jaunmuktane, Zane
Galasko, Douglas
Santana, Isabel
Tienari, Pentti J.
Myllykangas, Liisa
Oinas, Minna
Cairns, Nigel J.
Morris, John C.
Halliday, Glenda M.
Van Deerlin, Vivianna M.
Trojanowski, John Q.
Grassano, Maurizio
Calvo, Andrea
Mora, Gabriele
Canosa, Antonio
Floris, Gianluca
Bohannan, Ryan C.
Brett, Francesca
Gan-Or, Ziv
Geiger, Joshua T.
NATURE GENETICS, 2021, 53 (03) : 294 - +
[39] Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture
Ruth Chia
Marya S. Sabir
Sara Bandres-Ciga
Sara Saez-Atienzar
Regina H. Reynolds
Emil Gustavsson
Ronald L. Walton
Sarah Ahmed
Coralie Viollet
Jinhui Ding
Mary B. Makarious
Monica Diez-Fairen
Makayla K. Portley
Zalak Shah
Yevgeniya Abramzon
Dena G. Hernandez
Cornelis Blauwendraat
David J. Stone
John Eicher
Laura Parkkinen
Olaf Ansorge
Lorraine Clark
Lawrence S. Honig
Karen Marder
Afina Lemstra
Peter St George-Hyslop
Elisabet Londos
Kevin Morgan
Tammaryn Lashley
Thomas T. Warner
Zane Jaunmuktane
Douglas Galasko
Isabel Santana
Pentti J. Tienari
Liisa Myllykangas
Minna Oinas
Nigel J. Cairns
John C. Morris
Glenda M. Halliday
Vivianna M. Van Deerlin
John Q. Trojanowski
Maurizio Grassano
Andrea Calvo
Gabriele Mora
Antonio Canosa
Gianluca Floris
Ryan C. Bohannan
Francesca Brett
Ziv Gan-Or
Joshua T. Geiger
Nature Genetics, 2021, 53 : 294 - 303
[40] Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma
Sarin, Kavita Y.
Lin, Yuan
Daneshjou, Roxana
Ziyatdinov, Andrey
Thorleifsson, Gudmar
Rubin, Adam
Pardo, Luba M.
Wu, Wenting
Khavari, Paul A.
Uitterlinden, Andre
Nijsten, Tamar
Toland, Amanda E.
Olafsson, Jon H.
Sigurgeirsson, Bardur
Thorisdottir, Kristin
Jorgensen, Eric
Whittemore, Alice S.
Kraft, Peter
Stacey, Simon N.
Stefansson, Kari
Asgari, Maryam M.
Han, Jiali
NATURE COMMUNICATIONS, 2020, 11 (01)

← 1 2 3 4 5 →