Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.

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Version: Final published version
Serval ID
serval:BIB_69BB1F36F1D3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.
Journal
Human Molecular Genetics
Author(s)
Rahmioglu N., Macgregor S., Drong A.W., Hedman Å.K., Harris H.R., Randall J.C., Prokopenko I., Nyholt D.R., Nyholt D.R., Morris A.P., Montgomery G.W., Missmer S.A., Lindgren C.M., Zondervan K.T.
Working group(s)
International Endogene Consortium (IEC) The GIANT Consortium
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
2015
Volume
24
Number
4
Pages
1185-1199
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other.
Keywords
Adiposity/genetics, Adult, Alleles, Chromosomes, Human, Pair 7, Endometriosis/diagnosis, Endometriosis/etiology, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Obesity/complications, Obesity/genetics, Odds Ratio, Quantitative Trait Loci, Quantitative Trait, Heritable, Signal Transduction
Pubmed
Web of science
Open Access
Yes
Create date
20/11/2015 15:10
Last modification date
20/08/2019 15:24
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