Polygenic scores for handedness and their association with asymmetries in brain structure

Handedness is the most widely investigated motor preference in humans. The genetics of handedness and especially the link between genetic variation, brain structure, and right-left preference have not been investigated in detail. Recently, several well-powered genome-wide association studies (GWAS)...

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Bibliographic Details
Published in:Brain Structure and Function 2022-03, Vol.227 (2), p.515-527
Main Authors: Ocklenburg, Sebastian, Metzen, Dorothea, Schlüter, Caroline, Fraenz, Christoph, Arning, Larissa, Streit, Fabian, Güntürkün, Onur, Kumsta, Robert, Genç, Erhan
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Brain - diagnostic imaging
Cell Biology
Functional Laterality - genetics
Genetic diversity
Genome-wide association studies
Genome-Wide Association Study
Genomes
Handedness
Hemispheric laterality
Humans
Magnetic Resonance Imaging
Neuroimaging
Neurology
Neurosciences
Original
Original Article
Polygenic inheritance
Substantia grisea
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Summary:Handedness is the most widely investigated motor preference in humans. The genetics of handedness and especially the link between genetic variation, brain structure, and right-left preference have not been investigated in detail. Recently, several well-powered genome-wide association studies (GWAS) on handedness have been published, significantly advancing the understanding of the genetic determinants of left and right-handedness. In the present study, we estimated polygenic scores (PGS) of handedness-based on the GWAS by de Kovel and Francks (Sci Rep 9: 5986, 2019) in an independent validation cohort ( n  = 296). PGS reflect the sum effect of trait-associated alleles across many genetic loci. For the first time, we could show that these GWAS-based PGS are significantly associated with individual handedness lateralization quotients in an independent validation cohort. Additionally, we investigated whether handedness-derived polygenic scores are associated with asymmetries in gray matter macrostructure across the whole brain determined using magnetic resonance imaging. None of these associations reached significance after correction for multiple comparisons. Our results implicate that PGS obtained from large-scale handedness GWAS are significantly associated with individual handedness in smaller validation samples with more detailed phenotypic assessment.
ISSN:1863-2653
1863-2661
0340-2061
DOI:10.1007/s00429-021-02335-3