Abstract
Hand preference is a prominent behavioural trait linked to human brain asymmetry. A handful of genetic variants have been reported to associate with hand preference or quantitative measures related to it. Most of these reports were on the basis of limited sample sizes, by current standards for genetic analysis of complex traits. Here we performed a genome-wide association analysis of hand preference in the large, population-based UK Biobank cohort (N = 331,037). We used gene-set enrichment analysis to investigate whether genes involved in visceral asymmetry are particularly relevant to hand preference, following one previous report. We found no evidence supporting any of the previously suggested variants or genes, nor that genes involved in visceral laterality have a role in hand preference. It remains possible that some of the previously reported genes or pathways are relevant to hand preference as assessed in other ways, or else are relevant within specific disorder populations. However, some or all of the earlier findings are likely to be false positives, and none of them appear relevant to hand preference as defined categorically in the general population. Our analysis did produce a small number of novel, significant associations, including one implicating the microtubule-associated gene MAP2 in handedness.
Highlights
Hand preference is a prominent behavioural trait linked to human brain asymmetry
Genome-wide association scan (GWAS) analysis has not found any genomic locus with a large enough effect on hand preference to be compatible with monogenic models, unless there would be extensive genetic heterogeneity[25]
In the rare genetic disorder Primary Ciliary Dyskinesia (PCD)(MIM # 244400), recessive mutations in specific genes involved in ciliary biology result in a 50% chance of mirror-reversed left-right visceral asymmetry, a condition known as situs inversus totalis (SIT)[58]
Summary
Hand preference is a prominent behavioural trait linked to human brain asymmetry. A handful of genetic variants have been reported to associate with hand preference or quantitative measures related to it. The model proposed that there are two alleles, D (dextral) and C (chance), with the homozygous DD genotype producing right-handers (directional asymmetry), the homozygous CC genotype producing random asymmetry (50% right-handers and 50% left-handers) due to a hypothesized loss of direction-setting in brain development, and the heterozygote, DC, being intermediate and producing 25% left-handers and 75% right-handers Another related idea, conceived with respect to continuous measures of left-versus-right hand motor skill, was the ‘right-shift’ model, which proposed a major gene whose alleles cause either rightward mean asymmetry, or no directional bias[21]. Various molecular genetic studies have identified individual genes as potential contributing factors to handedness, with small effects, which would be consistent with a polygenic architecture underlying the heritable component to this trait. We review these genes briefly here: www.nature.com/scientificreports/
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