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

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_69BB1F36F1D3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci.
Périodique
Human Molecular Genetics
Auteur⸱e⸱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.
Collaborateur⸱rice⸱s
International Endogene Consortium (IEC) The GIANT Consortium
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Statut éditorial
Publié
Date de publication
2015
Volume
24
Numéro
4
Pages
1185-1199
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
20/11/2015 14:10
Dernière modification de la notice
20/08/2019 14:24
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