Most of us prefer to use one hand over the other. Surprisingly, hand preference is first observed during gestation as embryos begin to exhibit single arm movements. Across the lifespan, the consistent use of one hand leads to differences in the bone form and density. Preference for hand use has been extensively studied because of its relationship with language and the over-representation of left-handed people in some complex traits.
Most recently, two large-scale GWASs identified four genomic loci containing common variants of small effects associated with handedness. However, both GWASs failed to replicate signals at some genes that had previously been reported in smaller genetic associations.
In this study, researchers presented findings from the world’s largest genome-wide association (GWAS) meta-analysis of handedness to date. Researchers conducted a genome-wide association meta-analysis of handedness (N = 1,766,671) using the UK Biobank, 23andMe, and the International Handedness Consortium (IHC) data. Across all studies, the handedness phenotype was assessed by a questionnaire that evaluated which hand was used for writing or self-declared handedness. Combining data across the 32 IHC cohorts, 23andMe and UKBB yielded 1,534,836 right-handed individuals and 194,198 left-handed (11.0%) individuals. The meta-analysis identified 41 loci significantly associated with left-handedness. Some of these variants include rs4953572 near the FOXN2 gene, rs13107325 near the SLC39A8 gene, rs3132584 near the TUBB gene, rs12414988 near the BUB3 gene, rs9645660 near the CADM1 gene, rs1424114 near the SNTB2 gene, rs13006483 near the ITGAV, rs35551703 near the BPHL gene, and rs11820337 near the RSF1 gene. Furthermore, they found that seven variants associated with left-handedness were also associated with educational attainment. However, the direction of effect of these SNPs on left-handedness and educational attainment was not consistent. Interestingly, the genetic correlation between left-handedness and ambidexterity, the ability to perform the same action equally well with both hands, was low, suggesting that the genetic architecture underlying the two traits is different.
This world’s largest GWAS meta-analysis identified eight loci close to genes, such as the TUBB gene for rs3132584, involved in microtubule formation and regulation. With respect to handedness, microtubule proteins play important roles during the development and migration of neurons, plasticity, and neurodegenerative processes. The association between handedness and variation in microtubule genes also provides insights into differences in the prevalence of various neuropsychiatric disorders and left-handedness observed in some epidemiological studies. Read more about the study here: https://pubmed.ncbi.nlm.nih.gov/32989287/
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