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The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000-Genome imputed genotype data in up to ~370,000 women, we identify 389 independent signals (P<5×10-8) for age at menarche, a notable milestone in female pubertal development. In Icelandic data from deCODE, these signals explain ~7.4% of the population variance in age at menarche, corresponding to ~25% of the estimated heritability. We implicate ~250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects only when paternally inherited. Mendelian randomization analyses indicate causal inverse associations, independent of BMI, between puberty timing and risks for breast and endometrial cancers in women, and prostate cancer in men. In aggregate, our findings reveal new complexity in the genetic regulation of puberty timing and support causal links with cancer susceptibility.