To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10−60) and 9q31.2 (P = 2.2 × 10−33), we identified 30 new menarche loci (all P < 5 × 10−8) and found suggestive evidence for a further 10 loci (P < 1.9 × 10−6). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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Komen Breast Cancer Foundation; Swedish Foundation for Strategic Research (SSF); Swedish Heart-Lung Foundation; Swedish Ministry of Higher Education and Research; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (Ref: 33CSCO-122661, 3100AO-116323/1); the University of Bristol, University of Maryland General Clinical Research Center (M01 RR 16500); the Wellcome Trust (068545/Z/02, 076467/Z/05/Z, 077016/Z/05/Z, 89061/Z/09/Z, strategic award 079895); Western Australian DNA Bank; Western Australian Genetic Epidemiology Resource (see Supplementary Note for extended acknowledgments).
P.S., D.F.G., K.S. and U.T. are employed by deCODE Genetics. V.E. and A. Plump are employed by Merck & Co. V.M. and D.M.W. are employed by GlaxoSmithKline. A. Parker, L.Y. and K.T. are employed by Amgen. I.B. and spouse own stock in Incyte Ltd and GlaxoSmithKline.
A full list of members is provided in the Supplementary Note.
Supplementary Text and Figures
Supplementary Figures 1–8, Supplementary Tables 1–11 and 13–17 and Supplementary Note. (PDF 3142 kb)
Supplementary Table 12
Age at menarche associations for 8,770 SNPs in 16 candidate genes and their surrounding regions (+/-300kb). (XLS 1749 kb)
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Elks, C., Perry, J., Sulem, P. et al. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies. Nat Genet 42, 1077–1085 (2010). https://doi.org/10.1038/ng.714
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