Genome wide association analysis of age at menarche, menopause and menses cycle

初潮年龄（AAM）是一个复杂的性状，涉及遗传和环境因素。为了确定与AAM相关的遗传因素，我们对15,000多名日本女性样本进行了大规模的全基因组关联研究荟萃分析。在这里，我们确定了LIN 28 B基因座的SNP（单核苷酸多态性）rs364663与AAM之间的关联，P值为5.49 x10-7，效应量为0.089（年）。我们还评估了33个SNPs，这些SNPs以前被报道与欧洲血统女性的AAM相关。其中，TMEM 38 B中的两个SNPs rs 4452860和rs7028916与AAM有显著相关性（P = 0.0013，效应量为0.051），即使对这33个SNPs进行Bonferroni校正后也是如此。我们的研究结果阐明了遗传变异对日本人群AAM的影响。

Age at menarche (AAM) is a complex trait involving both genetic and environmental factors. To identify the genetic factors associated with AAM, we conducted a large scale meta-analysis of genome-wide association studies using more than15,000 Japanese female samples. Here we identified an association between SNP (single nucleotide polymorphism) rs364663 at the LIN28B locus and AAM, with a P-value of 5.49 x10-7 and an effect size of 0.089 (year). We also evaluated 33 SNPs that were previouslyreported to be associated with AAM in women of European ancestry. Among them, two SNPs rs4452860 and rs7028916 in TMEM38B indicated significant association with AAM in the same directions as reported in previous studies (P = 0.0013 with an effect size of0.051) even after Bonferroni correction for the 33 SNPs. Our findings elucidated the impact of genetic variations on AAM in the Japanese population.