A Variant in LIN288 Is Associated with 2D:4D Finger-Length Ratio, a Putative Retrospective Biomarker of Prenatal Testosterone Exposure
A Variant in LIN288 Is Associated with 2D:4D Finger-Length Ratio, a Putative Retrospective Biomarker of Prenatal Testosterone Exposure
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DOI：
10.1016/j.ajhg.2010.02.017
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发表时间：
2010-04-09
影响因子：
9.8
通讯作者：
Evans, David M.
中科院分区：
文献类型：
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作者：
Medland, Sarah E.;Zayats, Tetyana;Evans, David M.
个体第二至第四指长度的比率（2D：4D）通常用作产前雄激素暴露的非侵入性回顾性生物标志物。为了确定20：40的遗传决定因素，我们应用全基因组关联方法，从雅芳纵向研究的父母和孩子（ALSPAC），其中2D：4D比例已被测量的1507 11岁的儿童，以及从布里斯班青少年双胞胎研究的1382 12至16岁的样本。两次扫描的荟萃分析确定了LIN 28 B基因中的一个单一变异体，该变异体与2D：4D（rs314277：p = 4.1 x 10（-8））密切相关，随后在ALSPAC队列的另外3659名儿童中独立复制（p = 1.53 x 10（-6））。rs314277变异体的次要等位基因先前与身高增加和初潮年龄延迟有关，但在我们的研究中，它与20：4D增加有关，与先前关于2D：4D与初潮年龄之间相关性的报道相反。我们的研究结果质疑2D：4D作为产前睾酮暴露的简单回顾性生物标志物的有效性。
The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 20:40, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 x 10(-8)) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 x 10(-6)). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 20:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure.