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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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)
Verlagsversion Volltext
DOI
PMC
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
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Cited By
Cited By
Altmetric
6.677
1.583
18
18
Anmerkungen
Besondere Publikation
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Genome-wide Association; Body-mass Index; Cardiovascular-disease Risk; Waist-hip Ratio; Insulin-resistance; Metabolic Syndrome; Abdominal Obesity; Druggable Genome; Blood-pressure; Identifies 13
Sprache
englisch
Veröffentlichungsjahr
2014
HGF-Berichtsjahr
2014
ISSN (print) / ISBN
0964-6906
e-ISSN
1460-2083
Zeitschrift
Human Molecular Genetics
Quellenangaben
Band: 23,
Heft: 9,
Seiten: 2498-2510
Verlag
Oxford University Press
Verlagsort
Oxford
Begutachtungsstatus
Peer reviewed
Institut(e)
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
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
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