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

Stolk L, Perry JR, 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 EJ, Deary IJ, Dedoussis GV, Deloukas P, Ebrahim S, Eiriksdottir G, Emilsson V, Eriksson JG, Fauser BC, 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 AC, Johnson AD, Karasik D, Kardia SL, Keyzer J, Kiel DP, Kolcic I, Kutalik Z, Lahti J, Lai S, Laisk T, Laven JS, Lawlor DA, Liu J, Lopez LM, Louwers YV, Magnusson PK, Marongiu M, Martin NG, Klaric IM, Masciullo C, McKnight B, Medland SE, Melzer D, Mooser V, Navarro P, Newman AB, Nyholt DR, Onland-Moret NC, Palotie A, Paré G, Parker AN, Pedersen NL, Peeters PH, Pistis G, Plump AS, Polasek O, Pop VJ, Psaty BM, Räikkönen K, Rehnberg E, Rotter JI, Rudan I, Sala C, Salumets A, Scuteri A, Singleton A, Smith JA, Snieder H, Soranzo N, Stacey SN, Starr JM, Stathopoulou MG, Stirrups K, Stolk RP, Styrkarsdottir U, Sun YV, Tenesa A, Thorand B, Toniolo D, Tryggvadottir L, Tsui K, Ulivi S, van Dam RM, van der Schouw YT, van Gils CH, van Nierop P, Vink JM, Visscher PM, Voorhuis M, Waeber G, Wallaschofski H, Wichmann HE, Widen E, Wijnands-van Gent CJ, Willemsen G, Wilson JF, Wolffenbuttel BH, Wright AF, Yerges-Armstrong LM, Zemunik T, Zgaga L, Zillikens MC, Zygmunt M, LifeLines Cohort Study , Arnold AM, Boomsma DI, Buring JE, Crisponi L, Demerath EW, Gudnason V, Harris TB, Hu FB, Hunter DJ, Launer LJ, Metspalu A, Montgomery GW, Oostra BA, Ridker PM, Sanna S, Schlessinger D, Spector TD, Stefansson K, Streeten EA, Thorsteinsdottir U, Uda M, Uitterlinden AG, van Duijn CM, Völzke H, Murray A, Murabito JM, Visser JA, Lunetta KL

Nat. Genet. 44 (3) 260-268 [2012-01-22; online 2012-01-22]

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.

NGI Uppsala (SNP&SEQ Technology Platform)

National Genomics Infrastructure

PubMed 22267201

DOI 10.1038/ng.1051

Crossref 10.1038/ng.1051

pii: ng.1051
pmc: PMC3288642
mid: NIHMS342040