Genetic studies of body mass index yield new insights for obesity biology

被引：3201

作者：

Locke, Adam E. ^{[1
]}

Kahali, Bratati ^{[2
,3
]}

Berndt, Sonja I. ^{[4
]}

Justice, Anne E. ^{[5
]}

Pers, Tune H. ^{[6
,7
,8
,9
,10
,11
]}

Day, Felix R. ^{[12
]}

Powell, Corey ^{[2
,3
]}

Vedantam, Sailaja ^{[6
,7
,8
,9
]}

Buchkovich, Martin L. ^{[13
]}

Yang, Jian ^{[14
,15
]}

Croteau-Chonka, Damien C. ^{[13
,16
]}

Esko, Tonu ^{[6
,7
,8
,9
,10
,17
]}

Fall, Tove ^{[18
,19
,20
]}

Ferreira, Teresa ^{[21
]}

Gustafsson, Stefan ^{[19
,20
]}

Kutalik, Zoltan ^{[22
,23
,24
]}

Luan, Jian'an ^{[12
]}

Maegi, Reedik ^{[17
,21
]}

Randall, Joshua C. ^{[21
,25
]}

Winkler, Thomas W. ^{[26
]}

Wood, Andrew R. ^{[27
]}

Workalemahu, Tsegaselassie ^{[28
]}

Faul, Jessica D. ^{[29
]}

Smith, Jennifer A. ^{[30
]}

Zhao, Jing Hua ^{[12
]}

Zhao, Wei ^{[30
]}

Chen, Jin ^{[31
]}

Fehrmann, Rudolf ^{[32
]}

Hedman, Asa K. ^{[19
,20
,21
]}

Karjalainen, Juha ^{[32
]}

Schmidt, Ellen M. ^{[33
]}

Absher, Devin ^{[34
]}

Amin, Najaf ^{[35
]}

Anderson, Denise ^{[36
]}

Beekman, Marian ^{[37
,38
]}

Bolton, Jennifer L. ^{[39
]}

Bragg-Gresham, L. ^{[1
,40
]}

Buyske, Steven ^{[41
,42
]}

Demirkan, Ayse ^{[35
,43
]}

Deng, Guohong ^{[44
,45
,46
]}

Ehret, Georg B. ^{[47
,48
]}

Feenstra, Bjarke ^{[49
]}

Feitosa, Mary F. ^{[50
]}

Fischer, Krista ^{[17
]}

Goel, Anuj ^{[21
,51
]}

Gong, Jian ^{[52
]}

Jackson, Anne U. ^{[1
]}

Kanoni, Stavroula ^{[53
]}

Kleber, Marcus E. ^{[54
,55
]}

Kristiansson, Kati ^{[56
]}

机构：

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

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

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

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

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

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

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

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

[9] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA

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

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

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

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

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

[15] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4012, Australia

[16] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

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

[18] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden

[19] Uppsala Univ, Sci Life Lab, S-75185 Uppsala, Sweden

[20] Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden

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

[22] CHU Vaudois, Inst Social & Prevent Med IUMSP, CH-1010 Lausanne, Switzerland

[23] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[24] Univ Lausanne, Dept Med Genet, CH-1005 Lausanne, Switzerland

[25] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[26] Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany

[27] Univ Exeter, Univ Exeter Med Sch, Exeter EX1 2LU, Devon, England

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

[29] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA

[30] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA

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

[32] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands

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

[34] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA

[35] Erasmus MC Univ Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GE Rotterdam, Netherlands

[36] Univ Western Australia, Ctr Child Hlth Res, Telethon Inst Child Hlth Res, Perth, WA 6008, Australia

[37] Leiden Univ, Med Ctr, NCHA, NL-2300 RC Leiden, Netherlands

[38] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands

[39] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland

[40] Univ Michigan, Kidney Epidemiol & Cost Ctr, Ann Arbor, MI 48109 USA

[41] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ 08854 USA

[42] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA

[43] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands

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

[45] Univ London Imperial Coll Sci Technol & Med, Dept Gastroenterol & Hepatol, London W2 1PG, England

[46] Third Mil Med Univ, Southwest Hosp, Inst Infect Dis, Chongqing, Peoples R China

[47] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21205 USA

[48] Univ Hosp Geneva, Dept Specialties Internal Med, CH-1211 Geneva, Switzerland

[49] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark

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

来源：

NATURE | 2015年 / 518卷 / 7538期

关键词：

GENOME-WIDE ASSOCIATION; PROVIDES INSIGHTS; GLYCEMIC TRAITS; LOCI; METAANALYSIS; VARIANTS; INDIVIDUALS; HIPPOCAMPAL; ARCHITECTURE; TOPIRAMATE;

D O I：

10.1038/nature14177

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：

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

引用

页码：197 / +

页数：23

共 73 条

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