prior to menarche, or even prior to the onset of puberty would be required, but were unavailable in most studies. Further functional studies of these novel menarche loci may also help to clarify the biological mechanisms linking these traits. In addition to influencing the timing of pubertal initiation, sufficient adiposity is also required for the maintenance of normal hypothalamic-pituitary-gonadal function, via signalling by adipocytokines such as leptin36.Our pathway analyses highlighted Coenzyme A and fatty acid biosynthesis as biological pathways related to menarche timing. Hypothalamic levels of long-chain fatty acyl-Coenzyme As have been shown to regulate rodent feeding behaviour and glucose homeostasis37 and genetic variants in this pathway could therefore potentially alter central nutrient sensing.
