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

被引：485

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：

美国国家卫生研究院; 欧洲研究理事会; 英国惠康基金; 瑞典研究理事会; 英国医学研究理事会; 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

[21] Genome-Wide Linkage Analysis Identifies Loci for Physical Appearance Traits in Chickens
Sun, Yanfa
Liu, Ranran
Zhao, Guiping
Zheng, Maiqing
Sun, Yan
Yu, Xiaoqiong
Li, Peng
Wen, Jie
G3-GENES GENOMES GENETICS, 2015, 5 (10): : 2037 - 2041
[22] A Perception on Genome-Wide Genetic Analysis of Metabolic Traits in Arab Populations
Hebbar, Prashantha
Abubaker, Jehad Ahmed
Abu-Farha, Mohamed
Tuomilehto, Jaakko
Al-Mulla, Fahd
Thanaraj, Thangavel Alphonse
FRONTIERS IN ENDOCRINOLOGY, 2019, 10
[23] Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk
Jansen, Iris E.
Savage, Jeanne E.
Watanabe, Kyoko
Bryois, Julien
Williams, Dylan M.
Steinberg, Stacy
Sealock, Julia
Karlsson, Ida K.
Hagg, Sara
Athanasiu, Lavinia
Voyle, Nicola
Proitsi, Petroula
Witoelar, Aree
Stringer, Sven
Aarsland, Dag
Almdahl, Ina S.
Andersen, Fred
Bergh, Sverre
Bettella, Francesco
Bjornsson, Sigurbjorn
Braekhus, Anne
Brathen, Geir
de Leeuw, Christiaan
Desikan, Rahul S.
Djurovic, Srdjan
Dumitrescu, Logan
Fladby, Tormod
Hohman, Timothy J.
Jonsson, Palmi, V
Kiddle, Steven J.
Rongve, Arvid
Saltvedt, Ingvild
Sando, Sigrid B.
Selbaek, Geir
Shoai, Maryam
Skene, Nathan G.
Snaedal, Jon
Stordal, Eystein
Ulstein, Ingun D.
Wang, Yunpeng
White, Linda R.
Hardy, John
Hjerling-Leffler, Jens
Sullivan, Patrick F.
van der Flier, Wiesje M.
Dobson, Richard
Davis, Lea K.
Stefansson, Hreinn
Stefansson, Kari
Pedersen, Nancy L.
NATURE GENETICS, 2019, 51 (03) : 404 - +
[24] Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits
van Setten, Jessica
Verweij, Niek
Mbarek, Hamdi
Niemeijer, Maartje N.
Trompet, Stella
Arking, Dan E.
Brody, Jennifer A.
Gandin, Ilaria
Grarup, Niels
Hall, Leanne M.
Hemerich, Daiane
Lyytikainen, Leo-Pekka
Mei, Hao
Mueller-Nurasyid, Martina
Prins, Bram P.
Robino, Antonietta
Smith, Albert V.
Warren, Helen R.
Asselbergs, Folkert W.
Boomsma, Dorret I.
Caulfield, Mark J.
Eijgelsheim, Mark
Ford, Ian
Hansen, Torben
Harris, Tamara B.
Heckbert, Susan R.
Hottenga, Jouke-Jan
Iorio, Annamaria
Kors, Jan A.
Linneberg, Allan
MacFarlane, Peter W.
Meitinger, Thomas
Nelson, Christopher P.
Raitakari, Olli T.
Aldana, Claudia T. Silva
Sinagra, Gianfranco
Sinner, Moritz
Soliman, Elsayed Z.
Stoll, Monika
Uitterlinden, Andre
van Duijn, Cornelia M.
Waldenberger, Melanie
Alonso, Alvaro
Gasparini, Paolo
Gudnason, Vilmundur
Jamshidi, Yalda
Kaab, Stefan
Kanters, Jorgen K.
Lehtimaki, Terho
Munroe, Patricia B.
EUROPEAN JOURNAL OF HUMAN GENETICS, 2019, 27 (06) : 952 - 962
[25] Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease
Ge, Yi-Jun
Chen, Shi-Dong
Wu, Bang-Sheng
Zhang, Ya-Ru
Wang, Jun
He, Xiao-Yu
Liu, Wei-Shi
Chen, Yi-Lin
Ou, Ya-Nan
Shen, Xue-Ning
Huang, Yu-Yuan
Gan, Yi-Han
Yang, Liu
Ma, Ling-Zhi
Ma, Ya-Hui
Chen, Ke-Liang
Chen, Shu-Fen
Cui, Mei
Tan, Lan
Dong, Qiang
Zhao, Qian-Hua
Wang, Yan-Jiang
Jia, Jian-Ping
Yu, Jin-Tai
ALZHEIMERS & DEMENTIA, 2024, 20 (09) : 6243 - 6256
[26] Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci
Munz, Matthias
Richter, Gesa M.
Loos, Bruno G.
Jepsen, Soren
Divaris, Kimon
Offenbacher, Steven
Teumer, Alexander
Holtfreter, Birte
Kocher, Thomas
Bruckmann, Corinna
Jockel-Schneider, Yvonne
Graetz, Christian
Ahmad, Ilyas
Staufenbiel, Ingmar
van der Velde, Nathalie
Uitterlinden, Andre G.
de Groot, Lisette C. P. G. M.
Wellmann, Juergen
Berger, Klaus
Krone, Bastian
Hoffmann, Per
Laudes, Matthias
Lieb, Wolfgang
Franke, Andre
Erdmann, Jeanette
Dommisch, Henrik
Schaefer, Arne S.
EUROPEAN JOURNAL OF HUMAN GENETICS, 2019, 27 (01) : 102 - 113
[27] Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
Justice, Anne E.
Winkler, Thomas W.
Feitosa, Mary F.
Graff, Misa
Fisher, Virginia A.
Young, Kristin
Barata, Llilda
Deng, Xuan
Czajkowski, Jacek
Hadley, David
Ngwa, Julius S.
Ahluwalia, Tarunveer S.
Chu, Audrey Y.
Heard-Costa, Nancy L.
Lim, Elise
Perez, Jeremiah
Eicher, John D.
Kutalik, Zoltan
Xue, Luting
Mahajan, Anubha
Renstrom, Frida
Wu, Joseph
Qi, Qibin
Ahmad, Shafqat
Alfred, Tamuno
Amin, Najaf
Bielak, Lawrence F.
Bonnefond, Amelie
Bragg, Jennifer
Cadby, Gemma
Chittani, Martina
Coggeshall, Scott
Corre, Tanguy
Direk, Nese
Eriksson, Joel
Fischer, Krista
Gorski, Mathias
Harder, Marie Neergaard
Horikoshi, Momoko
Huang, Tao
Huffman, Jennifer E.
Jackson, Anne U.
Justesen, Johanne Marie
Kanoni, Stavroula
Kinnunen, Leena
Kleber, Marcus E.
Komulainen, Pirjo
Kumari, Meena
Lim, Unhee
Luan, Jian'an
NATURE COMMUNICATIONS, 2017, 8
[28] Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis
Corvol, Harriet
Blackman, Scott M.
Boelle, Pierre-Yves
Gallins, Paul J.
Pace, Rhonda G.
Stonebraker, Jaclyn R.
Accurso, Frank J.
Clement, Annick
Collaco, Joseph M.
Dang, Hong
Dang, Anthony T.
Franca, Arianna
Gong, Jiafen
Guillot, Loic
Keenan, Katherine
Li, Weili
Lin, Fan
Patrone, Michael V.
Raraigh, Karen S.
Sun, Lei
Zhou, Yi-Hui
O'Neal, Wanda K.
Sontag, Marci K.
Levy, Hara
Durie, Peter R.
Rommens, Johanna M.
Drumm, Mitchell L.
Wright, Fred A.
Strug, Lisa J.
Cutting, Garry R.
Knowles, Michael R.
NATURE COMMUNICATIONS, 2015, 6
[29] Genome-wide meta-analysis identifies new candidate genes for sickle cell disease nephropathy
Garrett, Melanie E.
Soldano, Karen L.
Erwin, Kyle N.
Zhang, Yingze
Gordeuk, Victor R.
Gladwin, Mark T.
Telen, Marilyn J.
Ashley-Koch, Allison E.
BLOOD ADVANCES, 2023, 7 (17) : 4782 - 4793
[30] Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma
Hysi, Pirro G.
Cheng, Ching-Yu
Springelkamp, Henriet
Macgregor, Stuart
Bailey, Jessica N. Cooke
Wojciechowski, Robert
Vitart, Veronique
Nag, Abhishek
Hewitt, Alex W.
Hohn, Rene
Venturini, Cristina
Mirshahi, Alireza
Ramdas, Wishal D.
Thorleifsson, Gudmar
Vithana, Eranga
Khor, Chiea-Chuen
Stefansson, Arni B.
Liao, Jiemin
Haines, Jonathan L.
Amin, Najaf
Wang, Ya Xing
Wild, Philipp S.
Ozel, Ayse B.
Li, Jun Z.
Fleck, Brian W.
Zeller, Tanja
Staffieri, Sandra E.
Teo, Yik-Ying
Cuellar-Partida, Gabriel
Luo, Xiaoyan
Allingham, R. Rand
Richards, Julia E.
Senft, Andrea
Karssen, Lennart C.
Zheng, Yingfeng
Bellenguez, Celine
Xu, Liang
Iglesias, Adriana I.
Wilson, James F.
Kang, Jae H.
van Leeuwen, Elisabeth M.
Jonsson, Vesteinn
Thorsteinsdottir, Unnur
Despriet, Dominiek D. G.
Ennis, Sarah
Moroi, Sayoko E.
Martin, Nicholas G.
Jansonius, Nomdo M.
Yazar, Seyhan
Tai, E-Shyong
NATURE GENETICS, 2014, 46 (10) : 1126 - 1130

← 1 2 3 4 5 →