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Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

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Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. / Brandler, William; Morris, Andrew; Evans, David; Scerri, Thomas; Kemp, John; Timpson, Nicholas; St Pourcain, Beate; Davey Smith, George; Ring, Susan; Stein, John; Monaco, Anthony; Talcott, Joel; Fisher, Simon; Webber, Caleb; Paracchini, Silvia.

In: PLoS Genetics, Vol. 9, No. 9, e10033751, 12.09.2013.

Research output: Contribution to journalArticle

Harvard

Brandler, W, Morris, A, Evans, D, Scerri, T, Kemp, J, Timpson, N, St Pourcain, B, Davey Smith, G, Ring, S, Stein, J, Monaco, A, Talcott, J, Fisher, S, Webber, C & Paracchini, S 2013, 'Common variants in left/right asymmetry genes and pathways are associated with relative hand skill' PLoS Genetics, vol. 9, no. 9, e10033751. https://doi.org/10.1371/journal.pgen.1003751

APA

Brandler, W., Morris, A., Evans, D., Scerri, T., Kemp, J., Timpson, N., ... Paracchini, S. (2013). Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. PLoS Genetics, 9(9), [e10033751]. https://doi.org/10.1371/journal.pgen.1003751

Vancouver

Brandler W, Morris A, Evans D, Scerri T, Kemp J, Timpson N et al. Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. PLoS Genetics. 2013 Sep 12;9(9). e10033751. https://doi.org/10.1371/journal.pgen.1003751

Author

Brandler, William ; Morris, Andrew ; Evans, David ; Scerri, Thomas ; Kemp, John ; Timpson, Nicholas ; St Pourcain, Beate ; Davey Smith, George ; Ring, Susan ; Stein, John ; Monaco, Anthony ; Talcott, Joel ; Fisher, Simon ; Webber, Caleb ; Paracchini, Silvia. / Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. In: PLoS Genetics. 2013 ; Vol. 9, No. 9.

Bibtex - Download

@article{f4631c7556d745b9b4ddfc8353077ec0,
title = "Common variants in left/right asymmetry genes and pathways are associated with relative hand skill",
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.",
author = "William Brandler and Andrew Morris and David Evans and Thomas Scerri and John Kemp and Nicholas Timpson and {St Pourcain}, Beate and {Davey Smith}, George and Susan Ring and John Stein and Anthony Monaco and Joel Talcott and Simon Fisher and Caleb Webber and Silvia Paracchini",
note = "This work was supported by the University of St Andrews, the UK Medical Research Council (grant number G0800523/86473 to SP), the Max Plank Society, and the the EU (Neurodys, 018696). Genotyping at the Wellcome Trust Centre for Human Genetics was supported by the Wellcome Trust (090532/Z/ 09/Z) and a Medical Research Council Hub Grant (G0900747 91070). Core support for ALSPAC was provided by the UK Medical Research Council and the Wellcome Trust (092731) and the University of Bristol. SP is a Royal Society University Research Fellow. CW is also funded by the UK Medical Research Funding and the EU (GENCODYS, 241995). APMor was supported by the Wellcome Trust (grant numbers WT075491, WT090532, and WT098017). WMB is the recipient of a Nuffield Department of Medicine Prize Studentship. JPK is funded by a Wellcome Trust PhD studentship (WT083431MA).",
year = "2013",
month = "9",
day = "12",
doi = "10.1371/journal.pgen.1003751",
language = "English",
volume = "9",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "9",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

AU - Brandler, William

AU - Morris, Andrew

AU - Evans, David

AU - Scerri, Thomas

AU - Kemp, John

AU - Timpson, Nicholas

AU - St Pourcain, Beate

AU - Davey Smith, George

AU - Ring, Susan

AU - Stein, John

AU - Monaco, Anthony

AU - Talcott, Joel

AU - Fisher, Simon

AU - Webber, Caleb

AU - Paracchini, Silvia

N1 - This work was supported by the University of St Andrews, the UK Medical Research Council (grant number G0800523/86473 to SP), the Max Plank Society, and the the EU (Neurodys, 018696). Genotyping at the Wellcome Trust Centre for Human Genetics was supported by the Wellcome Trust (090532/Z/ 09/Z) and a Medical Research Council Hub Grant (G0900747 91070). Core support for ALSPAC was provided by the UK Medical Research Council and the Wellcome Trust (092731) and the University of Bristol. SP is a Royal Society University Research Fellow. CW is also funded by the UK Medical Research Funding and the EU (GENCODYS, 241995). APMor was supported by the Wellcome Trust (grant numbers WT075491, WT090532, and WT098017). WMB is the recipient of a Nuffield Department of Medicine Prize Studentship. JPK is funded by a Wellcome Trust PhD studentship (WT083431MA).

PY - 2013/9/12

Y1 - 2013/9/12

N2 - 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.

AB - 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.

UR - http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003751

U2 - 10.1371/journal.pgen.1003751

DO - 10.1371/journal.pgen.1003751

M3 - Article

VL - 9

JO - PLoS Genetics

T2 - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 9

M1 - e10033751

ER -

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ID: 71542821