New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

被引：226

作者：

Lu, Yingchang ^{[1
,2
]}

Day, Felix R. ^{[3
]}

Gustafsson, Stefan ^{[4
,5
]}

Buchkovich, Martin L. ^{[6
]}

Na, Jianbo ^{[7
]}

Bataille, Veronique ^{[8
,9
]}

Cousminer, Diana L. ^{[10
]}

Dastani, Zari ^{[11
]}

Drong, Alexander W. ^{[12
]}

Esko, Tonu ^{[13
,14
,15
,16
,17
,18
]}

Evans, David M. ^{[19
,20
]}

Falchi, Mario ^{[9
,21
]}

Feitosa, Mary F. ^{[22
]}

Ferreira, Teresa ^{[12
]}

Hedman, Asa K. ^{[4
,5
,12
]}

Haring, Robin ^{[23
,24
]}

Hysi, Pirro G. ^{[9
]}

Iles, Mark M. ^{[25
]}

Justice, Anne E. ^{[26
]}

Kanoni, Stavroula ^{[27
,28
]}

Lagou, Vasiliki ^{[12
,29
]}

Li, Rui ^{[11
]}

Li, Xin ^{[30
]}

Locke, Adam ^{[31
]}

Lu, Chen ^{[32
]}

Magi, Reedik ^{[12
,13
]}

Perry, John R. B. ^{[3
]}

Pers, Tune H. ^{[15
,16
,17
,18
,33
,34
,35
]}

Qi, Qibin ^{[36
]}

Sanna, Marianna ^{[9
,21
]}

Schmidt, Ellen M. ^{[37
]}

Scott, William R. ^{[38
,39
]}

Shungin, Dmitry ^{[40
,41
,42
]}

Teumer, Alexander ^{[43
,44
]}

Vinkhuyzen, Anna A. E. ^{[45
]}

Walker, Ryan W. ^{[1
,2
]}

Westra, Harm-Jan ^{[46
,47
,48
,49
,50
]}

Zhang, Mingfeng ^{[51
]}

Zhang, Weihua ^{[38
,39
]}

Zhao, Jing Hua ^{[3
]}

Zhu, Zhihong ^{[45
]}

Afzal, Uzma ^{[38
,39
]}

Ahluwalia, Tarunveer Singh ^{[33
,52
,53
,54
]}

Bakker, Stephan J. L. ^{[55
]}

Bellis, Claire ^{[56
]}

Bonnefond, Amelie ^{[57
,58
,59
]}

Borodulin, Katja ^{[60
]}

Buchman, Aron S. ^{[61
]}

Cederholm, Tommy ^{[62
]}

Choh, Audrey C. ^{[63
]}

机构：

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

[2] Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA

[3] Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge CB2 0QQ, England

[4] Uppsala Univ, Sci Life Lab, S-75085 Uppsala, Sweden

[5] Uppsala Univ, Dept Med Sci, Mol Epidemiol, S-75185 Uppsala, Sweden

[6] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[7] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Biol, New York, NY 10029 USA

[8] West Herts NHS Trust, Hemel Hempstead HP2 4AD, Herts, England

[9] Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England

[10] Univ Helsinki, Inst Mol Med Finland, FI-00290 Helsinki, Finland

[11] McGill Univ, Jewish Gen Hosp, Lady Davis Inst, Dept Epidemiol Biostat & Human Genet, Montreal, PQ H3T 1E2, Canada

[12] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[13] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia

[14] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA

[15] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[16] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA

[17] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA

[18] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[19] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4102, Australia

[20] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England

[21] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London W12 0NN, England

[22] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA

[23] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany

[24] European Univ Appl Sci, Fac Appl Publ Hlth, D-18055 Rostock, Germany

[25] Univ Leeds, Canc Res UK Leeds Ctr, Leeds Inst Canc & Pathol, Leeds LS9 7TF, W Yorkshire, England

[26] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA

[27] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England

[28] Wellcome Trust Sanger Inst, Human Genet, Cambridge CB10 1SA, England

[29] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England

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

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

[32] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[33] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark

[34] Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA 02142 USA

[35] Statens Serum Inst, Dept Epidemiol Res, DK-2100 Copenhagen, Denmark

[36] Albert Einstein Coll Med, Dept Epidemiol & Popualt Hlth, Bronx, NY 10461 USA

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

[38] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London W2 1PG, England

[39] Ealing Hosp NHS Trust, Southall UB1 3HW, Middx, England

[40] Lund Univ, Ctr Diabet, Dept Clin Sci, Genet & Mol Epidemiol Unit,Skane Univ Hosptial, S-20502 Malmo, Sweden

[41] Umea Univ, Dept Publ Hlth & Clin Med, Med Unit, S-90187 Umea, Sweden

[42] Umea Univ, Dept Odontol, S-90185 Umea, Sweden

[43] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany

[44] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17475 Greifswald, Germany

[45] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

[46] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA

[47] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02446 USA

[48] Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02446 USA

[49] Harvard Univ, Sch Med, Boston, MA 02446 USA

[50] Partners Ctr Personalized Genet Med, Boston, MA 02446 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

瑞典研究理事会; 瑞士国家科学基金会; 英国医学研究理事会; 美国国家卫生研究院; 芬兰科学院; 美国食品与农业研究所; 英国惠康基金; 欧洲研究理事会; 加拿大健康研究院; 澳大利亚研究理事会; 俄罗斯基础研究基金会; 英国生物技术与生命科学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; MASS INDEX; COMMON VARIANTS; INSULIN-RESISTANCE; IDENTIFIES COMMON; PROVIDES INSIGHTS; GENETIC-VARIATION; ENERGY-BALANCE; EARLY-ONSET; APOE LOCUS;

D O I：

10.1038/ncomms10495

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P < 5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

引用

页数：15

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