Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations

被引：24

作者：

Yoneyama, Sachiko ^{[1
]}

Guo, Yiran ^{[3
,4
]}

Lanktree, Matthew B. ^{[5
]}

Barnes, Michael R. ^{[8
,11
]}

Elbers, Clara C. ^{[13
]}

Karczewski, Konrad J. ^{[14
]}

Padmanabhan, Sandosh ^{[15
]}

Bauer, Florianne ^{[13
]}

Baumert, Jens ^{[17
]}

Beitelshees, Amber ^{[20
]}

Berenson, Gerald S. ^{[23
]}

Boer, Jolanda M. A. ^{[24
]}

Burke, Gregory ^{[25
]}

Cade, Brian ^{[27
,28
]}

Chen, Wei ^{[23
]}

Cooper-Dehoff, Rhonda M. ^{[29
,30
]}

Gaunt, Tom R. ^{[31
]}

Gieger, Christian ^{[18
]}

Gong, Yan ^{[29
,30
]}

Gorski, Mathias ^{[32
,33
]}

Heard-Costa, Nancy ^{[34
]}

Johnson, Toby ^{[9
,10
,12
]}

Lamonte, Michael J. ^{[36
]}

Mcdonough, Caitrin ^{[29
,30
]}

Monda, Keri L. ^{[1
,37
]}

Onland-Moret, N. Charlotte ^{[13
]}

Nelson, Christopher P. ^{[38
,39
]}

O'Connell, Jeffrey R. ^{[21
]}

Ordovas, Jose ^{[40
]}

Peter, Inga ^{[41
]}

Peters, Annette ^{[17
]}

Shaffer, Jonathan ^{[42
]}

Shen, Haiqinq ^{[21
]}

Smith, Erin ^{[43
,44
]}

Speilotes, Liz ^{[45
,46
,47
,48
]}

Thomas, Fridtjof ^{[49
]}

Thorand, Barbara ^{[17
]}

Verschuren, W. M. Monique ^{[24
]}

Anand, Sonia S. ^{[6
,7
]}

Dominiczak, Anna ^{[16
]}

Davidson, Karina W. ^{[42
]}

Hegele, Robert A. ^{[50
]}

Heid, Iris ^{[18
,32
]}

Hofker, Marten H. ^{[51
]}

Huggins, Gordon S. ^{[52
]}

Illig, Thomas ^{[19
,53
]}

Johnson, Julie A. ^{[29
,30
]}

Kirkland, Susan ^{[54
]}

Koenig, Wolfgang ^{[55
]}

Langaee, Taimour Y. ^{[29
,30
]}

机构：

[1] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA

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

[3] Childrens Hosp Philadelphia, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA

[4] BGI Shenzhen, Shenzhen 518083, Peoples R China

[5] McMaster Univ, Dept Med, Hamilton, ON L8S 4L8, Canada

[6] McMaster Univ, Dept Med, Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON L8S 4L8, Canada

[7] McMaster Univ, Dept Clin Epidemiol, Populat Genom Program, Hamilton, ON L8S 4L8, Canada

[8] Queen Mary Univ London, Natl Inst Hlth Biomed Res Unit, London EC1M 6BQ, England

[9] Queen Mary Univ London, London EC1M 6BQ, England

[10] Queen Mary Univ London, Genome Ctr, William Harvey Res Inst, Barts, London EC1M 6BQ, England

[11] Queen Mary Univ London, London Sch Med, London EC1M 6BQ, England

[12] Queen Mary Univ London, London Sch Med & Dent, London EC1M 6BQ, England

[13] UMC Utrecht, Julius Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands

[14] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[15] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland

[16] Univ Glasgow, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland

[17] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, D-85764 Neuherberg, Germany

[18] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany

[19] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany

[20] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[21] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA

[22] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA

[23] Tulane Univ, Dept Epidemiol, New Orleans, LA 70112 USA

[24] Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, NL-3720 BA Bilthoven, Netherlands

[25] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA

[26] Wake Forest Univ, Sch Med, Look AHEAD Coordinating Ctr, Winston Salem, NC 27157 USA

[27] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA

[28] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA

[29] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA

[30] Univ Florida, Ctr Pharmacogen, Gainesville, FL 32610 USA

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

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

[33] Univ Med Ctr Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany

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

[35] Boston Univ, Sch Med, Framingham Heart Study, Boston, MA 02118 USA

[36] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Social & Prevent Med, Buffalo, NY 14214 USA

[37] Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA

[38] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England

[39] Glenfield Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England

[40] Tufts Univ, Nutr & Genom Lab, Boston, MA 02111 USA

[41] Mt Sinai, Icahn Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA

[42] Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, Div Gen Med, New York, NY 10032 USA

[43] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA

[44] Univ Calif San Diego, Sch Med, Radys Childrens Hosp, La Jolla, CA 92093 USA

[45] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

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

[47] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[48] Broad Inst, Cambridge, MA 02141 USA

[49] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA

[50] Univ Western Ontario, Schulich Sch Med & Dent, Robarts Res Inst, London, ON N6A 5C1, Canada

来源：

HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 09期

关键词：

GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; WAIST-HIP RATIO; CARDIOVASCULAR-DISEASE; ABDOMINAL OBESITY; BLOOD-PRESSURE; IDENTIFIES; 13; TISSUE; WEIGHT; MICE;

D O I：

10.1093/hmg/ddt626

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBIs Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 2080 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes 50 000 cosmopolitan tagged SNPs across 2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P 2.4 10(6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR ( SE, 0.048 0.008, P 7.7 10(9)) as was rs7302703-G in HOXC10 ( 0.044 0.008, P 2.9 10(7)) and rs936108-C in PEMT ( 0.035 0.007, P 1.9 10(6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 ( 0.10 0.02, P 1.9 10(6)) and rs1037575-A in ATBDB4 ( 0.046 0.01, P 2.2 10(6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

引用

页码：2498 / 2510

页数：13