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Gene-centric meta-analyses for central adiposity traits in up to 57412 individuals of European descent confirm known loci and reveal several novel associations.
Hum. Mol. Genet. 23, 2498-2510 (2014)
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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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide Association; Body-mass Index; Cardiovascular-disease Risk; Waist-hip Ratio; Insulin-resistance; Metabolic Syndrome; Abdominal Obesity; Druggable Genome; Blood-pressure; Identifies 13
Language
english
Publication Year
2014
HGF-reported in Year
2014
ISSN (print) / ISBN
0964-6906
e-ISSN
1460-2083
Journal
Human Molecular Genetics
Quellenangaben
Volume: 23,
Issue: 9,
Pages: 2498-2510
Publisher
Oxford University Press
Publishing Place
Oxford
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Genetic Epidemiology (IGE)
POF-Topic(s)
30202 - Environmental Health
30503 - Chronic Diseases of the Lung and Allergies
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504000-003
G-504000-002
G-504091-001
G-503900-001
G-504100-001
G-504000-001
G-504000-002
G-504091-001
G-503900-001
G-504100-001
G-504000-001
PubMed ID
24345515
WOS ID
WOS:000334359100023
Scopus ID
84897479338
Erfassungsdatum
2014-01-20