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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-07-01
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| Series: | Frontiers in Human Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnhum.2014.00473/full |
| _version_ | 1828910743558291456 |
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| author | Martine eHoogman Tulio eGuadalupe Marcel Peter Zwiers Patricia eKlarenbeek Clyde eFrancks Simon Edward Fisher |
| author_facet | Martine eHoogman Tulio eGuadalupe Marcel Peter Zwiers Patricia eKlarenbeek Clyde eFrancks Simon Edward Fisher |
| author_sort | Martine eHoogman |
| collection | DOAJ |
| 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 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 ten 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. |
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| format | Article |
| id | doaj.art-ec0192b379d54d88a54f207192a824e8 |
| institution | Directory Open Access Journal |
| issn | 1662-5161 |
| language | English |
| last_indexed | 2024-12-13T18:50:24Z |
| publishDate | 2014-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Human Neuroscience |
| spelling | doaj.art-ec0192b379d54d88a54f207192a824e82022-12-21T23:34:58ZengFrontiers Media S.A.Frontiers in Human Neuroscience1662-51612014-07-01810.3389/fnhum.2014.0047388990Assessing the effects of common variation in the FOXP2 gene on human brain structureMartine eHoogman0Tulio eGuadalupe1Marcel Peter Zwiers2Patricia eKlarenbeek3Clyde eFrancks4Simon Edward Fisher5Max Planck Institute for PsycholinguisticsMax Planck Institute for PsycholinguisticsDonders Institute for Cognitive NeuroimagingDonders Institute for Cognitive NeuroimagingMax Planck Institute for PsycholinguisticsMax Planck Institute for PsycholinguisticsThe 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 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 ten 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.http://journal.frontiersin.org/Journal/10.3389/fnhum.2014.00473/fullLanguageTranscription FactorsVBMimaging geneticsFoxP2brain anatomy |
| spellingShingle | Martine eHoogman Tulio eGuadalupe Marcel Peter Zwiers Patricia eKlarenbeek Clyde eFrancks Simon Edward Fisher Assessing the effects of common variation in the FOXP2 gene on human brain structure Frontiers in Human Neuroscience Language Transcription Factors VBM imaging genetics FoxP2 brain anatomy |
| title | 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_short | 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 |
| topic | Language Transcription Factors VBM imaging genetics FoxP2 brain anatomy |
| url | http://journal.frontiersin.org/Journal/10.3389/fnhum.2014.00473/full |
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