Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
Stolk L., Perry JRB., Chasman DI., He C., Mangino M., Sulem P., Barbalic M., Broer L., Byrne EM., Ernst F., Esko T., Franceschini N., Gudbjartsson DF., Hottenga JJ., Kraft P., McArdle PF., Porcu E., Shin SY., Smith AV., Van Wingerden S., Zhai G., Zhuang WV., Albrecht E., Alizadeh BZ., Aspelund T., Bandinelli S., Lauc LB., Beckmann JS., Boban M., Boerwinkle E., Broekmans FJ., Burri A., Campbell H., Chanock SJ., Chen C., Cornelis MC., Corre T., Coviello AD., D'Adamo P., Davies G., De Faire U., De Geus EJC., Deary IJ., Dedoussis GVZ., Deloukas P., Ebrahim S., Eiriksdottir G., Emilsson V., Eriksson JG., Fauser BCJM., Ferreli L., Ferrucci L., Fischer K., Folsom AR., Garcia ME., Gasparini P., Gieger C., Glazer N., Grobbee DE., Hall P., Haller T., Hankinson SE., Hass M., Hayward C., Heath AC., Hofman A., Ingelsson E., Janssens ACJW., Johnson AD., Karasik D., Kardia SLR., Keyzer J., Kiel DP., Kolcic I., Kutalik Z., Lahti J., Lai S., Laisk T.
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. © 2012 Nature America, Inc. All rights reserved.