PCSK6 is associated with handedness in individuals with dyslexia.
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.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
Thomas S
TS
Scerri
William M
WM
Brandler
Silvia
S
Paracchini
Andrew P
AP
Morris
Susan M
SM
Ring
Alex J
AJ
Richardson
Joel B
JB
Talcott
John
J
Stein
Anthony P
AP
Monaco
D004292:Dominance, Cerebral / Q000235:genetics*; D004410:Dyslexia / Q000235:genetics*; D007839:Functional Laterality / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D055457:Nodal Protein / Q000378:metabolism
D055457:Nodal Protein