Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Hum Mol Genet. 2011 Feb 1;20(3):608-14. doi: 10.1093/hmg/ddq475. Epub 2010 Nov 4.
Approximately 90% of humans are right-handed. Handedness is a heritable trait, yet the genetic basis is not well understood. Here we report a genome-wide association study for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)]. The most highly associated marker, rs11855415 (P = 4.7 × 10(-7)), is located within PCSK6. Two independent cohorts with RD show the same trend, with the minor allele conferring greater relative right-hand skill. Meta-analysis of all three RD samples is genome-wide significant (n = 744, P = 2.0 × 10(-8)). Conversely, in the general population (n = 2666), we observe a trend towards reduced laterality of hand skill for the minor allele (P = 0.0020). These results provide molecular evidence that cerebral asymmetry and dyslexia are linked. Furthermore, PCSK6 is a protease that cleaves the left-right axis determining protein NODAL. Functional studies of PCSK6 promise insights into mechanisms underlying cerebral lateralization and dyslexia.
大约 90%的人是右撇子。惯用手是一种可遗传的特征，但遗传基础尚不清楚。在这里，我们报告了一项针对阅读障碍（RD）个体相对手部技能的定量测量的全基因组关联研究。最相关的标记 rs11855415（P=4.7×10(-7)）位于 PCSK6 内。两个具有 RD 的独立队列都显示出相同的趋势，次要等位基因赋予更大的相对右手技能。所有三个 RD 样本的荟萃分析在全基因组范围内具有统计学意义（n=744，P=2.0×10(-8)）。相反，在普通人群（n=2666）中，我们观察到次要等位基因对手部技能的左右侧性降低的趋势（P=0.0020）。这些结果提供了分子证据，表明大脑不对称性和阅读障碍是相关的。此外，PCSK6 是一种蛋白酶，可切割左右轴决定蛋白 NODAL。PCSK6 的功能研究有望深入了解大脑偏侧化和阅读障碍的机制。
