Genome-wide association studies identify novel loci associated with age at menarche and age at natural menopause

Age at menarche and age at natural menopause are associated with causes of substantial morbidity and mortality such as breast cancer and cardiovascular disease. Studies have suggested both traits might be partially under genetic control. We performed a joint analysis of two genome-wide association studies of these two traits in a total of 17,438 women from the Nurses’ Health Study (NHS, N=2,287) and the Women’s Genome Health Study (WGHS, N=15,151). For age at menarche, we identified 10 associated SNPs (P=1×10(-7)-3×10(-13)) clustered at 6q21 (in or near the gene LIN28B) and 9q31.2 (in an intergenic region). For age at natural menopause, we identified 13 associated SNPs (P=1×10(-7)-1×10(-21)) clustered at 20p12.3 (in the gene MCM8), 19q13.42 (in or near the gene BRSK1), 5q35.2 (in or near genes RAP80 and HK3), and 6p24.2 (in the gene SYCP2L). These newly identified loci might expand understanding of the biological pathways regulating these two traits.