Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

被引：147

作者：

Justice, Anne E. ^{[1
]}

Winkler, Thomas W. ^{[2
]}

Feitosa, Mary F. ^{[3
]}

Graff, Misa ^{[1
]}

Fisher, Virginia A. ^{[4
]}

Young, Kristin ^{[1
]}

Barata, Llilda ^{[3
]}

Deng, Xuan ^{[4
]}

Czajkowski, Jacek ^{[3
]}

Hadley, David ^{[5
,6
]}

Ngwa, Julius S. ^{[4
,7
]}

Ahluwalia, Tarunveer S. ^{[8
,9
]}

Chu, Audrey Y. ^{[10
,11
,12
]}

Heard-Costa, Nancy L. ^{[10
,13
]}

Lim, Elise ^{[4
]}

Perez, Jeremiah ^{[4
]}

Eicher, John D. ^{[14
]}

Kutalik, Zoltan ^{[15
,16
,17
]}

Xue, Luting ^{[4
]}

Mahajan, Anubha ^{[18
]}

Renstrom, Frida ^{[19
,20
]}

Wu, Joseph ^{[4
]}

Qi, Qibin ^{[21
]}

Ahmad, Shafqat ^{[11
,12
,20
,22
]}

Alfred, Tamuno ^{[23
,24
]}

Amin, Najaf ^{[25
]}

Bielak, Lawrence F. ^{[26
]}

Bonnefond, Amelie ^{[27
]}

Bragg, Jennifer ^{[28
,29
,30
]}

Cadby, Gemma ^{[31
]}

Chittani, Martina ^{[32
]}

Coggeshall, Scott ^{[33
]}

Corre, Tanguy ^{[15
,16
,17
]}

Direk, Nese ^{[34
,35
]}

Eriksson, Joel ^{[36
]}

Fischer, Krista ^{[37
]}

Gorski, Mathias ^{[2
,38
]}

Harder, Marie Neergaard ^{[8
]}

Horikoshi, Momoko ^{[18
,39
]}

Huang, Tao ^{[22
,40
]}

Huffman, Jennifer E. ^{[14
,41
]}

Jackson, Anne U. ^{[29
,30
]}

Justesen, Johanne Marie ^{[8
]}

Kanoni, Stavroula ^{[42
]}

Kinnunen, Leena ^{[43
]}

Kleber, Marcus E. ^{[44
]}

Komulainen, Pirjo ^{[45
]}

Kumari, Meena ^{[46
,47
]}

Lim, Unhee ^{[48
]}

Luan, Jian'an ^{[49
]}

机构：

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

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

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

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

[5] St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England

[6] TransMed Syst Inc, Cupertino, CA 95014 USA

[7] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

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

[9] Steno Diabet Ctr, Gentofte, Denmark

[10] NHLBI Framingham Heart Study, Framingham, MA 01702 USA

[11] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[12] Harvard Med Sch, Boston, MA USA

[13] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA

[14] Framingham Heart Dis Epidemiol Study, NIH, Natl Heart Lung & Blood Inst, Populat Sci Branch, Framingham, MA USA

[15] CHU Vaudois, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland

[16] Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland

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

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

[19] Umea Univ, Dept Biobank Res, Umea, Sweden

[20] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden

[21] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA

[22] Harvard T H Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

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

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

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

[26] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA

[27] Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France

[28] Univ Michigan, Internal Med Nephrol, Ann Arbor, MI USA

[29] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA

[30] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[31] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Crawley 6009, Australia

[32] Univ Milan, Dept Hlth Sci, Via A Di Rudini 8, I-20142 Milan, Italy

[33] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

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

[35] Dokuz Eylul Univ, Dept Psychiat, Izmir, Turkey

[36] Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Gothenburg, Sweden

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

[38] Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany

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

[40] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Epidemiol Domain, Singapore 117549, Singapore

[41] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

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

[43] Natl Inst Hlth & Welfare, Dept Hlth, FI-00271 Helsinki, Finland

[44] Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany

[45] Kuopio Res Inst Exercise Med, Kuopio, Finland

[46] Univ Essex, ISER, Colchester CO4 3SQ, Essex, England

[47] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England

[48] Univ Hawaii, Canc Ctr, Epidemiol Program, Honolulu, HI 96813 USA

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

[50] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

瑞典研究理事会; 英国惠康基金; 英国医学研究理事会; 欧洲研究理事会; 美国国家卫生研究院; 俄罗斯基础研究基金会; 芬兰科学院; 瑞士国家科学基金会;

关键词：

OXIDATIVE STRESS; VITAMIN-C; ASSOCIATION; GENE; DEFICIENCY; IMPUTATION; PROTEINS; DISEASE; WEIGHT; MICE;

D O I：

10.1038/ncomms14977

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：

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

引用

页数：19

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