The strongest novel menarche signal was for rs1079866 (3.9 weeks/minor allele; 95% CI 2.9 to 5.0, P=5.5×10−14), approximately 250kb downstream of INHBA, which encodes the protein subunit Inhibin beta A. Heterodimers of Inhibin beta A and the Inhibin alpha subunit form the female reproductive hormone Inhibin A12. Inhibin A, produced by granulosa cells in the ovary, increases dramatically during pubertal development in girls13,14 and is involved in negative feedback regulation by inhibiting production of follicle stimulating hormone (FSH) by the pituitary and secretion of gonadotrophin releasing hormone (GnRH) from the hypothalamus15. Conversely, homodimers of Inhibin beta A form the hormone Activin A, which stimulates pituitary FSH production, and also exhibits a wide range of biological activities including the regulation of cellular proliferation and differentiation16.
