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Winkler, Thomas W. ; Heid, Iris M. ; Gorski, Mathias

The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study

Winkler, Thomas W., Heid, Iris M. und Gorski, Mathias (2015) The influence of age and sex on genetic associations with adult body size and shape: a large-scale genome-wide interaction study. PLoS Genetic 11 (10), e1005378.

Veröffentlichungsdatum dieses Volltextes: 02 Dez 2015 16:38
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.32444


Zusammenfassung

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants ...

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftPLoS Genetic
Verlag:PUBLIC LIBRARY SCIENCE
Ort der Veröffentlichung:SAN FRANCISCO
Band:11
Nummer des Zeitschriftenheftes oder des Kapitels:10
Seitenbereich:e1005378
Datum1 Oktober 2015
InstitutionenMedizin > Institut für Epidemiologie und Präventivmedizin
Identifikationsnummer
WertTyp
10.1371/journal.pgen.1005378DOI
Stichwörter / KeywordsSELF-REPORTED HEIGHT; FAT DISTRIBUTION; MASS INDEX; LIFE-COURSE; BIOLOGICAL PATHWAYS; NATURAL MENOPAUSE; PERIPHERAL-BLOOD; WEIGHT-GAIN; COMMON SNPS; LOCI
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-324447
Dokumenten-ID32444

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