Shared genetic aetiology of puberty timing between sexes and with health-related outcomes.
Shared genetic aetiology of puberty timing between sexes and with health-related outcomes.
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DOI：
10.1038/ncomms9842
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发表时间：
2015-11-09
影响因子：
16.6
通讯作者：
Perry JRB
中科院分区：
文献类型：
--
作者：
Day FR;Bulik-Sullivan B;Hinds DA;Finucane HK;Murabito JM;Tung JY;Ong KK;Perry JRB
对青春期时间的遗传调节的理解主要来自对罕见疾病的研究和基于女性的人群研究。在这里，我们报告了55，871名男性青春期时间的最大基因组分析，基于声音中断时的回忆年龄。对所有基因组变异的分析显示，男性和女性青春期时间之间存在强烈的遗传相关性（0.74，P=2.7 × 10−70）。然而，一些基因座显示出性别差异效应，包括在SIM 1/MCHR 2基因座上性别之间的方向相反效应（P异质性=1.6 × 10−12）。我们发现了五个新的青春期时间位点（P<5 × 10−8），除了先前在女性中报道的九个男性信号。新发现的相关基因包括两种视黄酸相关受体RORB和RXRA，以及两种据报道在罕见的青春期疾病中被破坏的基因LEPR和KAL 1。最后，我们确定了遗传相关性，表明青春期时间和体重指数，空腹胰岛素水平，血脂水平，2型糖尿病和心血管疾病之间的共同病因。过去对青春期遗传学的研究依赖于罕见的疾病或女性初潮的年龄。在这里，Day等人通过声音中断的年龄检查了男性的青春期时间，并发现了一些具有性二态效应和与其他健康状况共享的遗传结构的基因座。
Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10−70) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10−12). We find five novel loci for puberty timing (P<5 × 10−8), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease. Past studies on genetics of puberty relied on rare disorders or age of menarche in women. Here, Day et al. examine puberty timing in men by the age of voice breaking, and find some loci with sexually dimorphic effects and genetic architectures shared with other health conditions.