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
Creators: name: Yoneyama, Sachiko
name: Guo, Yiran
name: Lanktree, Matthew B.
name: Barnes, Michael R.
name: Elbers, Clara C.
name: Karczewski, Konrad J.
name: Padmanabhan, Sandosh
name: Bauer, Florianne
name: Baumert, Jens
name: Beitelshees, Amber
name: Berenson, Gerald S.
name: Boer, Jolanda M.A.
name: Burke, Gregory
name: Cade, Brian
name: Chen, Wei
name: Cooper-DeHoff, Rhonda M.
name: Gaunt, Tom R.
name: Gieger, Christian
name: Gong, Yan
name: Gorski, Mathias
name: Heard-Costa, Nancy
name: Johnson, Toby
name: Lamonte, Michael J.
name: Mcdonough, Caitrin
name: Monda, Keri L.
name: Onland-Moret, N. Charlotte
name: Nelson, Christopher P.
name: O’Connell, Jeffrey R.
name: Ordovas, Jose
name: Peter, Inga
name: Peters, Annette
name: Shaffer, Jonathan
name: Shen, Haiqinq
name: Smith, Erin
name: Speilotes, Liz
name: Thomas, Fridtjof
name: Thorand, Barbara
name: Verschuren, W. M. Monique
name: Anand, Sonia S.
name: Dominiczak, Anna
name: Davidson, Karina W.
name: Hegele, Robert A.
name: Heid, Iris
name: Hofker, Marten H.
name: Huggins, Gordon S.
name: Illig, Thomas
name: Johnson, Julie A.
name: Kirkland, Susan
name: Konig, Wolfgang
name: Langaee, Taimour Y.
name: Mccaffery, Jeanne
name: Melander, Olle
name: Mitchell, Braxton D.
name: Munroe, Patricia
name: Murray, Sarah S.
name: Papanicolaou, George
name: Redline, Susan
name: Reilly, Muredach
name: Samani, Nilesh J.
name: Schork, Nicholas J.
name: Van Der Schouw, Yvonne T.
name: Shimbo, Daichi
name: Shuldiner, Alan R.
name: Tobin, Martin D.
name: Wijmenga, Cisca
name: Yusuf, Salim
name: Hakonarson, Hakon
name: Lange, Leslie A.
name: Demerath, Ellen W.
name: Fox, Caroline S.
name: North, Kari E.
name: Reiner, Alex P.
name: Keating, Brendan
name: Taylor, Kira C.
name: Look AHEAD Research Group
name: GIANT Consortium
name: CARe IBC Consortium
Publisher: name: Columbia University
Year: 2013
Subjects: subject: Obesity--Genetic aspects
subject: Meta-analysis
subject: Adipose tissues--Analysis
subject: Genetics
subject: FOS: Biological sciences
subject: Medicine
subject: Medical sciences

description: 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 NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20 to 80. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ∼50,000 cosmopolitan tagged SNPs across ∼2,100 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&lt;2.4x10−6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β±SE,0.048±0.008, P=7.7x10−9) as was rs7302703-G in HOXC10 (β=0.044±0.008, P=2.9x10−7) and rs936108-C in PEMT (β=0.035±0.007, P=1.9x10−6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A near SHC1 (β=0.10±0.02, P=1.9x10−6), and rs1037575-A in ATBDB4 (β=0.046±0.01, P=2.2x10−6), 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.