Journal
HUMAN MOLECULAR GENETICS
Volume 20, Issue 3, Pages 608-614Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddq475
Keywords
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Funding
- Wellcome Trust [076566/Z/05/Z, 075491/Z/04, 076467]
- Medical Research Council [G0800523/86473]
- EU [018696]
- UK Medical Research Council [74882]
- University of Bristol
- MRC [G0800523] Funding Source: UKRI
- Medical Research Council [G9815508, G0800523] Funding Source: researchfish
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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 x 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 x 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.
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