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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways |
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| Authors: | Stolk Lisette Perry John R B Chasman Daniel I He Chunyan Mangino Massimo Sulem Patrick Barbalic Maja Broer Linda Byrne Enda M Ernst Florian Esko Tõnu Franceschini Nora Gudbjartsson Daniel F Hottenga Jouke-Jan Kraft Peter McArdle Patrick F Porcu Eleonora Shin So-Youn Smith Albert V van Wingerden Sophie Zhai Guangju Zhuang Wei V Albrecht Eva Alizadeh Behrooz Z Aspelund Thor Bandinelli Stefania Lauc Lovorka Barac Beckmann Jacques S Boban Mladen Boerwinkle Eric Broekmans Frank J Burri Andrea Campbell Harry Chanock Stephen J Chen Constance Cornelis Marilyn C Corre Tanguy Coviello Andrea D |
| Institution: | Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. |
| 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(-8)). 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-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause. |
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