While our pathway analyses strongly identified potential new biological pathways involved in pubertal timing, we acknowledge that the ability to assign putative functions to these menarche loci is substantially limited by the lack of identification of the causal variant at each locus. Many of the strongest associated SNPs were located 100’s of kb distant to the nearest gene, and some menarche loci contained several plausible genes. Indeed, none of the top signals represented non-synonymous SNPs, and only two were in LD with such variants (in OLFM2 and TRIM66). Use of eQTLs helped to identify the likely causal genes (GAB2, RBM6 and NARG2) at three menarche loci that spanned multiple genes. However, much future work will be required to identify the causal variants and implicated genes related to these menarche loci.
