Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics

Ninety per cent of the human population has been right-handed since the Paleolithic, yet the brain signature and genetic basis of handedness remain poorly characterized. Here, we correlated brain imaging phenotypes from ∼9000 UK Biobank participants with handedness, and with loci found significantly...

Full description

Bibliographic Details
Main Authors: Wiberg, A, Ng, M, Al Omran, Y, Alfaro-Almagro, F, McCarthy, P, Marchini, J, Bennett, DL, Smith, S, Douaud, G, Furniss, D
Format: Journal article
Published: Oxford University Press 2019
_version_ 1797105431522312192
author Wiberg, A
Ng, M
Al Omran, Y
Alfaro-Almagro, F
McCarthy, P
Marchini, J
Bennett, DL
Smith, S
Douaud, G
Furniss, D
author_facet Wiberg, A
Ng, M
Al Omran, Y
Alfaro-Almagro, F
McCarthy, P
Marchini, J
Bennett, DL
Smith, S
Douaud, G
Furniss, D
author_sort Wiberg, A
collection OXFORD
description Ninety per cent of the human population has been right-handed since the Paleolithic, yet the brain signature and genetic basis of handedness remain poorly characterized. Here, we correlated brain imaging phenotypes from ∼9000 UK Biobank participants with handedness, and with loci found significantly associated with handedness after we performed genome-wide association studies (GWAS) in ∼400 000 of these participants. Our imaging–handedness analysis revealed an increase in functional connectivity between left and right language networks in left-handers. GWAS of handedness uncovered four significant loci (rs199512, rs45608532, rs13017199, and rs3094128), three of which are in—or expression quantitative trait loci of—genes encoding proteins involved in brain development and patterning. These included microtubule-related MAP2 and MAPT, as well as WNT3 and MICB, all implicated in the pathogenesis of diseases such as Parkinson’s, Alzheimer’s and schizophrenia. In particular, with rs199512, we identified a common genetic influence on handedness, psychiatric phenotypes, Parkinson’s disease, and the integrity of white matter tracts connecting the same language-related regions identified in the handedness–imaging analysis. This study has identified in the general population genome-wide significant loci for human handedness in, and expression quantitative trait loci of, genes associated with brain development, microtubules and patterning. We suggest that these genetic variants contribute to neurodevelopmental lateralization of brain organization, which in turn influences both the handedness phenotype and the predisposition to develop certain neurological and psychiatric diseases.
first_indexed 2024-03-07T06:47:27Z
format Journal article
id oxford-uuid:fb581e8c-005f-42c1-b346-19b4467a00b5
institution University of Oxford
last_indexed 2024-03-07T06:47:27Z
publishDate 2019
publisher Oxford University Press
record_format dspace
spelling oxford-uuid:fb581e8c-005f-42c1-b346-19b4467a00b52022-03-27T13:13:06ZHandedness, language areas and neuropsychiatric diseases: insights from brain imaging and geneticsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fb581e8c-005f-42c1-b346-19b4467a00b5Symplectic Elements at OxfordOxford University Press2019Wiberg, ANg, MAl Omran, YAlfaro-Almagro, FMcCarthy, PMarchini, JBennett, DLSmith, SDouaud, GFurniss, DNinety per cent of the human population has been right-handed since the Paleolithic, yet the brain signature and genetic basis of handedness remain poorly characterized. Here, we correlated brain imaging phenotypes from ∼9000 UK Biobank participants with handedness, and with loci found significantly associated with handedness after we performed genome-wide association studies (GWAS) in ∼400 000 of these participants. Our imaging–handedness analysis revealed an increase in functional connectivity between left and right language networks in left-handers. GWAS of handedness uncovered four significant loci (rs199512, rs45608532, rs13017199, and rs3094128), three of which are in—or expression quantitative trait loci of—genes encoding proteins involved in brain development and patterning. These included microtubule-related MAP2 and MAPT, as well as WNT3 and MICB, all implicated in the pathogenesis of diseases such as Parkinson’s, Alzheimer’s and schizophrenia. In particular, with rs199512, we identified a common genetic influence on handedness, psychiatric phenotypes, Parkinson’s disease, and the integrity of white matter tracts connecting the same language-related regions identified in the handedness–imaging analysis. This study has identified in the general population genome-wide significant loci for human handedness in, and expression quantitative trait loci of, genes associated with brain development, microtubules and patterning. We suggest that these genetic variants contribute to neurodevelopmental lateralization of brain organization, which in turn influences both the handedness phenotype and the predisposition to develop certain neurological and psychiatric diseases.
spellingShingle Wiberg, A
Ng, M
Al Omran, Y
Alfaro-Almagro, F
McCarthy, P
Marchini, J
Bennett, DL
Smith, S
Douaud, G
Furniss, D
Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics
title Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics
title_full Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics
title_fullStr Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics
title_full_unstemmed Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics
title_short Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics
title_sort handedness language areas and neuropsychiatric diseases insights from brain imaging and genetics
work_keys_str_mv AT wiberga handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT ngm handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT alomrany handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT alfaroalmagrof handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT mccarthyp handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT marchinij handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT bennettdl handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT smiths handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT douaudg handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics
AT furnissd handednesslanguageareasandneuropsychiatricdiseasesinsightsfrombrainimagingandgenetics