Assessing the effects of common variation in the FOXP2 gene on human brain structure

The FOXP2 transcription factor is one of the most well-known genes to have been implicated in developmental speech and language disorders. Rare mutations disrupting the function of this gene have been described in different families and cases. In a large three-generation family carrying a missense m...

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Main Authors: Hoogman, Martine, Guadalupe, Tulio, Zwiers, Marcel P., Klarenbeek, Patricia, Francks, Clyde, Fisher, Simon E.
Format: Online
Language:English
Published: Frontiers Media S.A. 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076884/
id pubmed-4076884
recordtype oai_dc
spelling pubmed-40768842014-07-10 Assessing the effects of common variation in the FOXP2 gene on human brain structure Hoogman, Martine Guadalupe, Tulio Zwiers, Marcel P. Klarenbeek, Patricia Francks, Clyde Fisher, Simon E. Neuroscience The FOXP2 transcription factor is one of the most well-known genes to have been implicated in developmental speech and language disorders. Rare mutations disrupting the function of this gene have been described in different families and cases. In a large three-generation family carrying a missense mutation, neuroimaging studies revealed significant effects on brain structure and function, most notably in the inferior frontal gyrus, caudate nucleus, and cerebellum. After the identification of rare disruptive FOXP2 variants impacting on brain structure, several reports proposed that common variants at this locus may also have detectable effects on the brain, extending beyond disorder into normal phenotypic variation. These neuroimaging genetics studies used groups of between 14 and 96 participants. The current study assessed effects of common FOXP2 variants on neuroanatomy using voxel-based morphometry (VBM) and volumetric techniques in a sample of >1300 people from the general population. In a first targeted stage we analyzed single nucleotide polymorphisms (SNPs) claimed to have effects in prior smaller studies (rs2253478, rs12533005, rs2396753, rs6980093, rs7784315, rs17137124, rs10230558, rs7782412, rs1456031), beginning with regions proposed in the relevant papers, then assessing impact across the entire brain. In the second gene-wide stage, we tested all common FOXP2 variation, focusing on volumetry of those regions most strongly implicated from analyses of rare disruptive mutations. Despite using a sample that is more than 10 times that used for prior studies of common FOXP2 variation, we found no evidence for effects of SNPs on variability in neuroanatomy in the general population. Thus, the impact of this gene on brain structure may be largely limited to extreme cases of rare disruptive alleles. Alternatively, effects of common variants at this gene exist but are too subtle to be detected with standard volumetric techniques. Frontiers Media S.A. 2014-07-01 /pmc/articles/PMC4076884/ /pubmed/25013396 http://dx.doi.org/10.3389/fnhum.2014.00473 Text en Copyright © 2014 Hoogman, Guadalupe, Zwiers, Klarenbeek, Francks and Fisher. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Hoogman, Martine
Guadalupe, Tulio
Zwiers, Marcel P.
Klarenbeek, Patricia
Francks, Clyde
Fisher, Simon E.
spellingShingle Hoogman, Martine
Guadalupe, Tulio
Zwiers, Marcel P.
Klarenbeek, Patricia
Francks, Clyde
Fisher, Simon E.
Assessing the effects of common variation in the FOXP2 gene on human brain structure
author_facet Hoogman, Martine
Guadalupe, Tulio
Zwiers, Marcel P.
Klarenbeek, Patricia
Francks, Clyde
Fisher, Simon E.
author_sort Hoogman, Martine
title Assessing the effects of common variation in the FOXP2 gene on human brain structure
title_short Assessing the effects of common variation in the FOXP2 gene on human brain structure
title_full Assessing the effects of common variation in the FOXP2 gene on human brain structure
title_fullStr Assessing the effects of common variation in the FOXP2 gene on human brain structure
title_full_unstemmed Assessing the effects of common variation in the FOXP2 gene on human brain structure
title_sort assessing the effects of common variation in the foxp2 gene on human brain structure
description The FOXP2 transcription factor is one of the most well-known genes to have been implicated in developmental speech and language disorders. Rare mutations disrupting the function of this gene have been described in different families and cases. In a large three-generation family carrying a missense mutation, neuroimaging studies revealed significant effects on brain structure and function, most notably in the inferior frontal gyrus, caudate nucleus, and cerebellum. After the identification of rare disruptive FOXP2 variants impacting on brain structure, several reports proposed that common variants at this locus may also have detectable effects on the brain, extending beyond disorder into normal phenotypic variation. These neuroimaging genetics studies used groups of between 14 and 96 participants. The current study assessed effects of common FOXP2 variants on neuroanatomy using voxel-based morphometry (VBM) and volumetric techniques in a sample of >1300 people from the general population. In a first targeted stage we analyzed single nucleotide polymorphisms (SNPs) claimed to have effects in prior smaller studies (rs2253478, rs12533005, rs2396753, rs6980093, rs7784315, rs17137124, rs10230558, rs7782412, rs1456031), beginning with regions proposed in the relevant papers, then assessing impact across the entire brain. In the second gene-wide stage, we tested all common FOXP2 variation, focusing on volumetry of those regions most strongly implicated from analyses of rare disruptive mutations. Despite using a sample that is more than 10 times that used for prior studies of common FOXP2 variation, we found no evidence for effects of SNPs on variability in neuroanatomy in the general population. Thus, the impact of this gene on brain structure may be largely limited to extreme cases of rare disruptive alleles. Alternatively, effects of common variants at this gene exist but are too subtle to be detected with standard volumetric techniques.
publisher Frontiers Media S.A.
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076884/
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