Population genetic differentiation of height and body mass index across Europe

被引：140

作者：

Robinson, Matthew R. ^{[1
]}

Hemani, Gibran ^{[1
]}

Medina-Gomez, Carolina ^{[2
]}

Mezzavilla, Massimo ^{[3
,4
]}

Esko-, Tonu ^{[5
,6
,7
,8
]}

Shakhbazov, Konstantin ^{[1
]}

Powell, Joseph E. ^{[1
,9
]}

Vinkhuyzen, Anna ^{[1
]}

Berndt, Sonja I. ^{[10
]}

Gustafsson, Stefan ^{[11
]}

Justice, Anne E. ^{[12
]}

Kahali, Bratati ^{[13
,14
]}

Locke, Adam E. ^{[15
]}

Pers, Tune H. ^{[6
,7
,8
,16
]}

Vedantam, Sailaja ^{[6
,7
]}

Wood, Andrew R.

van Rheenen, Wouter ^{[18
]}

Andreassen, Ole A. ^{[19
,20
]}

Gasparini, Paolo ^{[3
]}

Metspalu, Andres ^{[5
]}

van den Berg, Leonard H. ^{[18
]}

Veldink, Jan H. ^{[18
]}

Rivadeneira, Fernando ^{[2
]}

Werge, Thomas M. ^{[21
,22
,23
]}

Abecasis, Goncalo R. ^{[15
]}

Boomsma, Dorret I. ^{[24
,25
,26
]}

Chasman, Daniel I. ^{[8
,27
]}

de Geus, Eco J. C. ^{[24
,25
,26
]}

Frayling, Timothy M. ^{[17
]}

Hirschhorn, Joel N. ^{[5
,6
,7
,8
]}

Hottenga, Jouke Jan ^{[24
,25
,26
]}

Ingelsson, Erik ^{[28
]}

Loos, Ruth J. F. ^{[29
,30
,31
,32
]}

Magnusson, Patrik K. E. ^{[33
]}

Martin, Nicholas G. ^{[34
]}

Montgomery, Grant W. ^{[34
]}

North, Kari E. ^{[13
,14
,35
]}

Pedersen, Nancy L. ^{[33
]}

Spector, Timothy D. ^{[36
]}

Speliotes, Elizabeth K. ^{[15
]}

Goddard, Michael E. ^{[37
,38
]}

Yang, Jian ^{[1
,9
]}

Visscher, Peter M. ^{[1
,9
]}

机构：

[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[2] Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands

[3] Ist Ricovero & Cura Carattere Sci IRCCS, Inst Maternal & Child Hlth, Trieste, Italy

[4] Wellcome Trust Sanger Inst, Hinxton, Cambs, England

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

[6] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA

[7] Broad Inst MIT & Harvard, Cambridge, MA USA

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

[9] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia

[10] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

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

[12] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA

[13] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA

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

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

[16] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark

[17] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England

[18] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands

[19] Univ Oslo, Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway

[20] Univ Oslo, Inst Clin Med, Oslo, Norway

[21] Mental Hlth Devices Copenhagen, MHC Sct Hans, Inst Biol Psychiat, Roskilde, Denmark

[22] Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci, Copenhagen, Denmark

[23] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark

[24] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands

[25] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands

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

[27] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA

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

[29] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, MRC,Epidemiol Unit, Cambridge CB2 2QQ, England

[30] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[31] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA

[32] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA

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

[34] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[35] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA

[36] Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[37] Dept Primary Ind, Biosci Res Div, Melbourne, Vic, Australia

[38] Univ Melbourne, Dept Food & Agr Syst, Melbourne, Vic, Australia

来源：

NATURE GENETICS | 2015年 / 47卷 / 11期

基金：

澳大利亚国家健康与医学研究理事会; 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; 美国国家卫生研究院; 欧洲研究理事会; 英国惠康基金;

关键词：

NATURAL-SELECTION; SYSTEMATIC ANALYSIS; CHRONIC DISEASES; GLOBAL VARIATION; COMMON SNPS; BURDEN; MORTALITY; HEALTH; ASSOCIATION; INSIGHTS;

D O I：

10.1038/ng.3401

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Across-nation differences in the mean values for complex traits are common(1-8), but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 x 10(-8); BMI, P < 5.95 x 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).

引用

页码：1357 / +

页数：8

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