Among the confirmed novel menarche loci were several loci implicated in body weight regulation, including four loci with established associations with BMI (in/near FTO, SEC16B, TRA2B and TMEM18). Furthermore, our systematic analysis of established BMI-related SNPs showed that the majority of alleles related to higher BMI and waist-hip ratio also showed at least nominal associations with earlier menarche (Table 2). It is noteworthy that three novel menarche loci are in/near genes implicated in energy homeostasis in animal models (BSX, CRTC1, and MCHR2). In the GIANT consortium data, we did not detect any associations between these loci and adult BMI however the BSX and MCHR2 loci were nominally associated with adult height. In order to robustly investigate whether menarche loci have pleiotropic effects on growth, or whether the association with menarche timing is driven through increased adiposity, measures of body fatness 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
