Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

• Type of Material: Article
• Authors: Lisette Stolk, Erasmus MC; John R B Perry, University of Exeter; Daniel I Chasman, Brigham and Women’s Hospital; Chunyan He, Indiana University School of Medicine; Massimo Mangino, Kings College London; Patrick Sulem, deCODE Genetics; Maja Barbalic, University of Texas Health Science Center at Houston; Linda Broer, Erasmus MC; Enda M Byrne, Queensland Institute of Medical Research; Florian Ernst, Universität Greifswald; Tonu Esko, University of Tartu; Nora Franceschini, University of North Carolina; Daniel F Gudbjartsson, deCODE Genetics; Jouke-Jan Hottenga, Vrije Universiteit Amsterdam; Peter Kraft, Harvard University; Patrick F McArdle, University of Maryland; Eleonora Porcu, Consiglio Nazionale delle Ricerche; So-Youn Shin, Wellcome Trust Sanger Institute; A Cecile Janssens, Emory University; Yan Sun, Emory University
• Language: English
• Date: 2012-03-01
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Nature America, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/ng.1051
• Title of Journal or Parent Work: Nature Genetics
• ISSN: 1061-4036
• Volume: 44
• Issue: 3
• Start Page: 260
• End Page: U55
• Keywords: GENE-EXPRESSION; MUTATION; Genetics & Heredity; POLYMORPHISMS; PREMATURE OVARIAN FAILURE; FOLLICLE-STIMULATING-HORMONE; GENOME-WIDE ASSOCIATION; ONSET; PROTEIN; NATURAL MENOPAUSE; Life Sciences & Biomedicine; DISEASE; Science & Technology
• Research Categories: Health Sciences, Obstetrics and Gynecology; Biology, Genetics

Abstract

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 - 10 g8). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-I °B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.