Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Nat Genet. 2010 Dec;42(12):1077-85. doi: 10.1038/ng.714.
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.
为了确定初潮年龄的相关基因座，我们对 87802 名欧洲血统女性进行了 32 项全基因组关联研究的荟萃分析，并在最多 14731 名女性中进行了验证。除了已知的 LIN28B（P=5.4×10⁻⁶⁰）和 9q31.2（P=2.2×10⁻³³）位点外，我们还确定了 30 个新的初潮相关基因座（所有 P<5×10⁻⁸），并发现另外 10 个基因座存在显著关联（P<1.9×10⁻⁶）。新的基因座包括四个先前与体重指数相关的基因座（FTO、SEC16B、TRA2B 和 TMEM18 内或附近）、三个位于或接近其他与能量稳态相关的基因座（BSX、CRTC1 和 MCHR2）以及三个位于或接近与激素调节相关的基因座（INHBA、PCSK2 和 RXRG）。Ingenuity 和基因集富集途径分析确定辅酶 A 和脂肪酸生物合成是与初潮时间相关的生物学过程。
