DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.
Détails
Télécharger: BIB_92D295068C5A.P001.pdf (263.92 [Ko])
Etat: Public
Version: de l'auteur⸱e
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_92D295068C5A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
DNA mismatch repair gene MSH6 implicated in determining age at natural menopause.
Périodique
Human Molecular Genetics
Collaborateur⸱rice⸱s
kConFab investigators, ReproGen Consortium
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Statut éditorial
Publié
Date de publication
2014
Volume
23
Numéro
9
Pages
2490-2497
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
The length of female reproductive lifespan is associated with multiple adverse outcomes, including breast cancer, cardiovascular disease and infertility. The biological processes that govern the timing of the beginning and end of reproductive life are not well understood. Genetic variants are known to contribute to ∼50% of the variation in both age at menarche and menopause, but to date the known genes explain <15% of the genetic component. We have used genome-wide association in a bivariate meta-analysis of both traits to identify genes involved in determining reproductive lifespan. We observed significant genetic correlation between the two traits using genome-wide complex trait analysis. However, we found no robust statistical evidence for individual variants with an effect on both traits. A novel association with age at menopause was detected for a variant rs1800932 in the mismatch repair gene MSH6 (P = 1.9 × 10(-9)), which was also associated with altered expression levels of MSH6 mRNA in multiple tissues. This study contributes to the growing evidence that DNA repair processes play a key role in ovarian ageing and could be an important therapeutic target for infertility.
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/05/2014 16:56
Dernière modification de la notice
20/08/2019 14:55