Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill

Brandler, William M., Morris, Andrew P., Evans, David M., Scerri, Thomas S., Kemp, John P., Timpson, Nicholas J., St Pourcain, Beate, Smith, George Davey, Ring, Susan M., Stein, John, Monaco, Anthony P., Talcott, Joel B., Fisher, Simon E., Webber, Caleb and Paracchini, Silvia (2013) Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill. PLoS Genetics, 9 9: e100375.1-e100375.11. doi:10.1371/journal.pgen.1003751


Author Brandler, William M.
Morris, Andrew P.
Evans, David M.
Scerri, Thomas S.
Kemp, John P.
Timpson, Nicholas J.
St Pourcain, Beate
Smith, George Davey
Ring, Susan M.
Stein, John
Monaco, Anthony P.
Talcott, Joel B.
Fisher, Simon E.
Webber, Caleb
Paracchini, Silvia
Title Common Variants in Left/Right Asymmetry Genes and Pathways Are Associated with Relative Hand Skill
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2013
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1003751
Open Access Status DOI
Volume 9
Issue 9
Start page e100375.1
End page e100375.11
Total pages 11
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2014
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1105 Dentistry
1306 Cancer Research
2716 Genetics (clinical)
Abstract Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10-9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 19 Mar 2014, 16:02:49 EST by Kylie Hengst on behalf of UQ Diamantina Institute