In the majority of studies contributing to this report, age at menarche was recalled several years later, and often to the nearest completed whole year. Although recalled age at menarche is valid40, and is unlikely to show systematic bias by genotype, any non-differential error would lead to reduced statistical power. Menarche indicates the completion of puberty in females and it is unclear whether our novel menarche loci also influence timing of other pubertal phenotypes. The known menarche locus in LIN28B was shown to also influence the onset of breast development in girls, the timing of pubic hair development and voice breaking in boys9, and the timing of the pubertal growth spurt in both boys and girls41. While our novel menarche loci might also regulate such wider pubertal processes, it is plausible that some (e.g. INHBA) might have sex-specific effects. Our study was restricted to cohorts of European ancestry and our results are therefore not generalized to other groups. African American girls tend to show earlier pubertal maturation compared to girls of White European ancestry42 and genetic studies in such populations might reveal different menarche loci.
