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Randall, Joshua C. ; Winkler, Thomas W. ; Heid, Iris M.

Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits

Article

Randall, Joshua C., Winkler, Thomas W. and Heid, Iris M. (2013) Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits. PLoS genetics 9 (6), e1003500.

DOI to cite this document: 10.5283/epub.28782


Abstract

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of ...

Given the anthropometric differences between men and women and previous evidence of sex-difference in genetic effects, we conducted a genome-wide search for sexually dimorphic associations with height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip-ratio (133,723 individuals) and took forward 348 SNPs into follow-up (additional 137,052 individuals) in a total of 94 studies. Seven loci displayed significant sex-difference (FDR<5%), including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were genome-wide significant in women (P<5x10(-8)), but not in men. Sex-differences were apparent only for waist phenotypes, not for height, weight, BMI, or hip circumference. Moreover, we found no evidence for genetic effects with opposite directions in men versus women. The PPARG locus is of specific interest due to its role in diabetes genetics and therapy. Our results demonstrate the value of sex-specific GWAS to unravel the sexually dimorphic genetic underpinning of complex traits.



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Details

Item typeArticle
Journal or Publication TitlePLoS genetics
PublisherPUBLIC LIBRARY SCIENCE
Open Access TypeGold (with APC)
Place of PublicationSAN FRANCISCO
Volume9
Number of Issue or Book Chapter6
Page Rangee1003500
Date6 June 2013
Date of publication03 Sep 2013 09:47
InstitutionsMedicine > Institut für Epidemiologie und Präventivmedizin
Identification Number
ValueType
23754948PubMed ID
10.1371/journal.pgen.1003500DOI
KeywordsBODY-MASS INDEX; WAIST-HIP RATIO; FAT DISTRIBUTION; ENZYME-ACTIVITIES; ADULT HEIGHT; PPAR-GAMMA; RISK; VARIANTS; METAANALYSIS; OBESITY;
Dewey Decimal Classification600 Technology > 610 Medical sciences Medicine
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-287820
Item ID28782

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