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

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title = "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",
abstract = "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.",
author = "Sachiko Yoneyama and Yiran Guo and Lanktree, {Matthew B.} and Barnes, {Michael R.} and Elbers, {Clara C.} and Karczewski, {Konrad J.} and Sandosh Padmanabhan and Florianne Bauer and Jens Baumert and Amber Beitelshees and Berenson, {Gerald S.} and Boer, {Jolanda M. A.} and Gregory Burke and Brian Cade and Wei Chen and Cooper-Dehoff, {Rhonda M.} and Gaunt, {Tom R.} and Christian Gieger and Yan Gong and Mathias Gorski and Nancy Heard-Costa and Toby Johnson and Lamonte, {Michael J.} and Caitrin Mcdonough and Monda, {Keri L.} and Onland-Moret, {N. Charlotte} and Nelson, {Christopher P.} and O'Connell, {Jeffrey R.} and Jose Ordovas and Inga Peter and Annette Peters and Jonathan Shaffer and Haiqinq Shen and Erin Smith and Liz Speilotes and Fridtjof Thomas and Barbara Thorand and Verschuren, {W. M. Monique} and Anand, {Sonia S.} and Anna Dominiczak and Davidson, {Karina W.} and Hegele, {Robert A.} and Iris Heid and Hofker, {Marten H.} and Huggins, {Gordon S.} and Thomas Illig and Johnson, {Julie A.} and Susan Kirkland and Wolfgang Koenig and Langaee, {Taimour Y.} and Jeanne Mccaffery and Olle Melander and Mitchell, {Braxton D.} and Patricia Munroe and Murray, {Sarah S.} and George Papanicolaou and Susan Redline and Muredach Reilly and Samani, {Nilesh J.} and Schork, {Nicholas J.} and {Van der Schouw}, {Yvonne T.} and Daichi Shimbo and Shuldiner, {Alan R.} and Tobin, {Martin D.} and Cisca Wijmenga and Salim Yusuf and Hakon Hakonarson and Lange, {Leslie A.} and Demerath, {Ellen W.} and Fox, {Caroline S.} and North, {Kari E.} and Reiner, {Alex P.} and Brendan Keating and Taylor, {Kira C.}",
year = "2014",
doi = "10.1093/hmg/ddt626",
language = "English",
volume = "23",
pages = "2498--2510",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "9",