Polygenic scores for handedness and their association with asymmetries in brain structure
Abstract 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 latest GWAS by de Kovel and Francks (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 can significantly predict individual handedness lateralization quotients in an independent validation cohort. Additionally, we investigated whether handedness-derived polygenic scores can predict asymmetries in gray matter macrostructure across the whole brain determined using magnetic resonance imaging. Our results indicate that none of these predictions reached significance after correction for multiple comparisons. This indicates that the genetic determinants of handedness are only weakly associated with structural asymmetries in gray matter. Other brain phenotypes may link genetic variation to handedness.