Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

被引：151

作者：

Graff, Mariaelisa ^{[1
]}

Scott, Robert A. ^{[2
]}

Justice, Anne E. ^{[1
]}

Young, Kristin L. ^{[1
,3
]}

Feitosa, Mary F. ^{[4
]}

Barata, Llilda ^{[4
]}

Winkler, Thomas W. ^{[5
]}

Chu, Audrey Y. ^{[6
,7
]}

Mahajan, Anubha ^{[8
]}

Hadley, David ^{[9
]}

Xue, Luting ^{[6
,10
]}

Workalemahu, Tsegaselassie ^{[11
]}

Heard-Costa, Nancy L. ^{[6
,12
]}

den Hoed, Marcel ^{[2
,13
,14
]}

Ahluwalia, Tarunveer S. ^{[15
,16
]}

Qi, Qibin ^{[17
]}

Ngwa, Julius S. ^{[18
]}

Renstrom, Frida ^{[19
,20
]}

Quaye, Lydia ^{[21
]}

Eicher, John D. ^{[22
]}

Hayes, James E. ^{[23
,24
]}

Cornelis, Marilyn ^{[11
,25
,26
,27
]}

Kutalik, Zoltan ^{[28
,29
]}

Lim, Elise ^{[10
]}

Luan, Jian'an ^{[2
]}

Huffman, Jennifer E. ^{[6
,30
]}

Zhang, Weihua ^{[31
,32
]}

Zhao, Wei ^{[33
]}

Griffin, Paula J. ^{[10
]}

Haller, Toomas ^{[34
]}

Ahmad, Shafqat ^{[19
]}

Marques-Vidal, Pedro M. ^{[35
]}

Bien, Stephanie ^{[36
]}

Yengo, Loic ^{[37
]}

Teumer, Alexander ^{[38
,39
]}

Smith, Albert Vernon ^{[40
,41
]}

Kumari, Meena ^{[42
]}

Harder, Marie Neergaard ^{[15
]}

Justesen, Johanne Marie ^{[15
]}

Kleber, Marcus E. ^{[43
,44
]}

Hollensted, Mette ^{[15
]}

Lohman, Kurt ^{[45
]}

Rivera, Natalia V. ^{[46
]}

Whitfield, John B. ^{[47
]}

Zhao, Jing Hua ^{[2
]}

Stringham, Heather M. ^{[48
]}

Lyytikainen, Leo-Pekka ^{[49
,50
]}

Huppertz, Charlotte ^{[51
,52
,53
,54
]}

Willemsen, Gonneke ^{[51
,52
,53
]}

Peyrot, Wouter J. ^{[55
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA

[2] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England

[3] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA

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

[5] Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany

[6] Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA

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

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

[9] St Georges Univ London, Div Populat Hlth Sci & Educ, London, England

[10] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA

[11] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA

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

[13] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden

[14] Uppsala Univ, Sci Life Lab, Uppsala, Sweden

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

[16] Steno Diabet Ctr, Gentofte, Denmark

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

[18] Howard Univ, Dept Internal Med, Washington, DC 20059 USA

[19] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden

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

[21] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England

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

[23] Cornell Univ, Weill Cornell Grad Sch Med Sci, Cell & Dev Biol Grad Program, New York, NY 10021 USA

[24] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA

[25] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA

[26] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, 75 Francis St, Boston, MA 02115 USA

[27] Harvard Med Sch, Boston, MA USA

[28] Lausanne Univ Hosp, Inst Social & Prevent Med, Lausanne, Switzerland

[29] Swiss Inst Bioinformat, Lausanne, Switzerland

[30] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[31] Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[32] Ealing Hosp HNS Trust, Dept Cardiol, Middlesex, England

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

[34] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia

[35] Lausanne Univ Hosp, Dept Internal Med, Internal Med, Lausanne, Switzerland

[36] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA

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

[38] Univ Med Greifswald, Inst Community Med, Greifswald, Germany

[39] DZHK, German Ctr Cardiovasc Res, Greifswald, Germany

[40] Iceland Heart Assoc, Kopavogur, Iceland

[41] Univ Iceland, Fac Med, Reykjavik, Iceland

[42] Univ Essex, ISER, Colchester, Essex, England

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

[44] Friedrich Schiller Univ Jena, Inst Nutr, Jena, Germany

[45] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA

[46] Karolinska Inst, Resp Unit, Dept Med Solna, Stockholm, Sweden

[47] QIMR Berghofer Med Res Inst, Genet Epidemiol, Brisbane, Qld, Australia

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

[49] Fimlab Labs, Dept Clin Chem, Tampere, Finland

[50] Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland

来源：

PLOS GENETICS | 2017年 / 13卷 / 04期

基金：

英国惠康基金; 瑞典研究理事会; 英国医学研究理事会; 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; 加拿大健康研究院; 加拿大创新基金会;

关键词：

BODY-MASS INDEX; REACTIVE PROTEIN-LEVELS; GENE-EXPRESSION; ASSOCIATION METAANALYSIS; BINDING PROTEIN; FOOD-INTAKE; OBESITY; FAT; VARIANTS; POLYMORPHISM;

D O I：

10.1371/journal.pgen.1006528

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

引用

页数：26

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