Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600 (IMPH), Nashville, TN 37203-1738, USA.
Hum Reprod. 2013 Apr;28(4):1135-43. doi: 10.1093/humrep/det011. Epub 2013 Feb 12.
Do genetic polymorphisms which influence age at menarche in women of European ancestry also influence women of Chinese ancestry?
Many genetic variants influencing age at menarche in European populations appear to impact Chinese populations in a similar manner.
Prior genome-wide association studies have uncovered 42 SNPs associated with age at menarche in European populations. This study is the first to demonstrate that many of the genetic determinants of age at menarche are shared between European and Chinese women.
We evaluated 37 of 42 SNPs identified as associated with age at menarche from a recent, large meta-analysis, consisting primarily of women of European ancestry, in a population of 6929 Chinese women from Shanghai, China. We also constructed weighted genetic risk scores (GRSs) combining the number of effect variants for all 37 SNPs, or only the SNPs associated with age at menarche among our study population, to evaluate their joint influence on age at menarche.
For 32 of the 37 evaluated variants, the direction of the allele associations were the same between women of European ancestry and women of Chinese ancestry (P = 3.71 × 10(-6), binomial sign test); 9 of these were statistically significant. Subjects in the highest quintile of GRSs began menarche ∼5 months later than those in the lowest quintile. BIAS, LIMITATIONS AND GENERALIZABILITY TO OTHER POPULATIONS: Age at menarche was obtained by self-report, which can be subject to recall errors. The current analysis was restricted to loci which met or approached GWAS significance thresholds and did not evaluate loci which may act predominantly or exclusively in the Chinese population. The smaller sample size for our meta-analysis compared with meta-analyses conducted in European populations reduced the power to detect significant results.
STUDY FUNDING/COMPETING INTERESTS: This study was supported, in part, by grants from US National Institutes of Health (grants R01CA124558, R01CA090899, R01CA070867; R01CA064277 and R01CA092585 and UL1 RR024975), Ingram professorship funds and Allen Foundation funds. There are no competing interests to declare.
影响欧洲裔女性初潮年龄的遗传多态性是否也会影响华裔女性？
影响欧洲人群初潮年龄的许多遗传变异似乎以类似的方式影响中国人群。
先前的全基因组关联研究已经发现 42 个与欧洲人群初潮年龄相关的 SNP。本研究首次证明，许多初潮年龄的遗传决定因素在欧洲和中国女性之间是共有的。
我们评估了最近一项大型荟萃分析中确定的与初潮年龄相关的 42 个 SNP 中的 37 个，该分析主要由欧洲血统的女性组成，在来自中国上海的 6929 名中国女性中进行。我们还构建了加权遗传风险评分（GRS），将所有 37 个 SNP 的效应变异数量或仅与我们研究人群中初潮年龄相关的 SNP 进行组合，以评估它们对初潮年龄的共同影响。
在评估的 37 个变体中，有 32 个变体在欧洲裔女性和华裔女性中的等位基因关联方向相同（P = 3.71×10（-6），二项式符号检验）；其中 9 个具有统计学意义。GRS 最高五分位组的受试者初潮时间比最低五分位组晚约 5 个月。
偏倚、局限性和对其他人群的普遍性：初潮年龄通过自我报告获得，可能存在回忆错误。本分析仅限于达到或接近 GWAS 显著性阈值的基因座，并且没有评估可能主要或专门在华裔人群中起作用的基因座。与在欧洲人群中进行的荟萃分析相比，我们的荟萃分析样本量较小，降低了检测显著结果的能力。
研究资金/利益冲突：本研究部分得到美国国立卫生研究院（R01CA124558、R01CA090899、R01CA064277 和 R01CA092585 以及 UL1 RR024975 拨款、英格拉姆教授职位基金和艾伦基金会基金）的资助。没有竞争利益需要申报。
