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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.

Thursday,2014-05-29 14:56 America/Los_Angeles — poolea2
TitleGene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.
Publication TypeJournal Article
Year of Publication2014
AuthorsYoneyama, S, Guo, Y, Lanktree, MB, Barnes, MR, Elbers, CC, Karczewski, KJ, Padmanabhan, S, Bauer, F, Baumert, J, Beitelshees, A, Berenson, GS, Boer, JMA, Burke, G, Cade, B, Chen, W, Cooper-Dehoff, RM, Gaunt, TR, Gieger, C, Gong, Y, Gorski, M, Heard-Costa, N, Johnson, T, Lamonte, MJ, McDonough, C, Monda, KL, Onland-Moret, CN, Nelson, CP, O'Connell, JR, Ordovas, J, Peter, I, Peters, A, Shaffer, J, Shen, H, Smith, E, Speilotes, L, Thomas, F, Thorand, B, Verschuren, WMMonique, Anand, SS, Dominiczak, A, Davidson, KW, Hegele, RA, Heid, I, Hofker, MH, Huggins, GS, Illig, T, Johnson, JA, Kirkland, S, König, W, Langaee, TY, McCaffery, J, Melander, O, Mitchell, BD, Munroe, P, Murray, SS, Papanicolaou, G, Redline, S, Reilly, M, Samani, NJ, Schork, NJ, van der Schouw, YT, Shimbo, D, Shuldiner, AR, Tobin, MD, Wijmenga, C, Yusuf, S, Hakonarson, H, Lange, LA, Demerath, EW, Fox, CS, North, KE, Reiner, AP, Keating, B, Taylor, KC
Corporate/Institutional AuthorsLook AHEAD Research Group, GIANT Consortium, CARe IBC Consortium
JournalHum Mol Genet
Volume23
Issue9
Pagination2498-510
Date Published2014 May 01
ISSN1460-2083
KeywordsAdiposity, Adult, Aged, Aged, 80 and over, Body Mass Index, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Waist Circumference, Waist-Hip Ratio, Young Adult
Abstract<p>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 20-80 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 (β ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (β = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (β = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (β = 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. </p>
DOI10.1093/hmg/ddt626
Alternate JournalHum. Mol. Genet.
PubMed ID24345515
PubMed Central IDPMC3988452
Grant ListUL1 RR025774 / RR / NCRR NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
R01 HL088119 / HL / NHLBI NIH HHS / United States
N01-HC-95162 / HC / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
UL1 TR000064 / TR / NCATS NIH HHS / United States
RG/07/005/23633 / / British Heart Foundation / United Kingdom
N01-HC-48047 / HC / NHLBI NIH HHS / United States
U01 HL72515 / HL / NHLBI NIH HHS / United States
U01 HG007416 / HG / NHGRI NIH HHS / United States
U01 GM074492 / GM / NIGMS NIH HHS / United States
N01-HC-95163 / HC / NHLBI NIH HHS / United States
N01-HC-95168 / HC / NHLBI NIH HHS / United States
UL1-RR-024156 / RR / NCRR NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
N01-HC-95095 / HC / NHLBI NIH HHS / United States
N01-HC-95165 / HC / NHLBI NIH HHS / United States
R01 AG016592 / AG / NIA NIH HHS / United States
R01 ES021724 / ES / NIEHS NIH HHS / United States
N01-HC-48050 / HC / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
P30 DK072488 / DK / NIDDK NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
N01-HC-95164 / HC / NHLBI NIH HHS / United States
PG/07/131/24254 / / British Heart Foundation / United Kingdom
SP/08/005/25115 / / British Heart Foundation / United Kingdom
N01-HC-48049 / HC / NHLBI NIH HHS / United States
K24 HL084034 / HL / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
N01-HC-95160 / HC / NHLBI NIH HHS / United States
U01 DK057131 / DK / NIDDK NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
HD-062783 / HD / NICHD NIH HHS / United States
G0902313 / / Medical Research Council / United Kingdom
U01 GM074518 / GM / NIGMS NIH HHS / United States
N01-HC-95161 / HC / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
N01-HC-48048 / HC / NHLBI NIH HHS / United States
N01-HC-95166 / HC / NHLBI NIH HHS / United States
HD-061437 / HD / NICHD NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
MC_UU_12013/8 / / Medical Research Council / United Kingdom
N01-HC-95167 / HC / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
N01 HC55222 / HC / NHLBI NIH HHS / United States
P30 DK017047 / DK / NIDDK NIH HHS / United States
N01-HC-65226 / HC / NHLBI NIH HHS / United States

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