DNA mismatch repair gene MSH6 implicated in determining age at natural menopause

Perry JR, Hsu YH, Chasman DI, Johnson AD, Elks C, Albrecht E, Andrulis IL, Beesley J, Berenson GS, Bergmann S, Bojesen SE, Bolla MK, Brown J, Buring JE, Campbell H, Chang-Claude J, Chenevix-Trench G, Corre T, Couch FJ, Cox A, Czene K, d'Adamo AP, Davies G, Deary IJ, Dennis J, Easton DF, Engelhardt EG, Eriksson JG, Esko T, Fasching P, Figueroa JD, Flyger H, Fraser A, Garcia-Closas M, Gasparini P, Gieger C, Giles G, Guenel P, Hagg S, Hall P, Hayward C, Hopper J, Ingelsson E, kConFab i, Kardia SL, Kasiman K, Knight JA, Lahti J, Lawlor DA, Magnusson PK, Margolin S, Marsh JA, Metspalu A, Olson JE, Pennell CE, Polasek O, Rahman I, Ridker PM, Robino A, Rudan I, Rudolph A, Salumets A, Schmidt MK, Schoemaker MJ, Smith EN, Smith JA, Southey M, Stockl D, Swerdlow AJ, Thompson DJ, Truong T, Ulivi S, Waldenberger M, Wang Q, Wild S, Wilson JF, Wright AF, Zgaga L, ReproGen C, Ong KK, Murabito JM, Karasik D, Murray A (2014) DNA mismatch repair gene MSH6 implicated in determining age at natural menopause. Hum Mol Genet

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 about 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="" (gcta).="" 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="1.9x10-9)," 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="">