Reacción a "Reactions to study linking rare genetic variants with left-handedness"

In this study they have investigated rare genetic variants (i.e. with a frequency of less than 1% in the population) that may be associated with left-handedness. This is a novel approach, as until now common genetic variation has been studied, which has identified that some genes related to the cytoskeleton (microtubules) may be associated with left-handedness.  

In this case, exome data (protein-coding part of the genome) from the UK Biobank database was used. The large sample size (with thousands of individuals sequenced: more than 38,000 left-handed and more than 313,000 right-handed) has allowed them to focus on this type of rare genetic variation, allowing them to identify a gene (TUBB4B, also related to microtubules) that contains 2.7 more mutations of this type in left-handers than in right-handers.  

This study therefore complements previous studies and indicates that rare genetic variation involving changes at the protein level also plays a role in left-handedness. In addition, the gene identified is closely related to those indicated by the other genetic studies, highlighting the possible role of microtubules.  

Left or right hand dominance (left-handedness) is established early in development and, for most people, the right hand is more dominant. This suggests that there is probably a genetic basis and is the motivation for these studies on the genetic basis of left-handedness. 

However, it is worth noting that the studies conducted so far, including this one, have very low heritability estimates (proportion of variance explained by genetic variation): 0.9-5% depending on the study. Twin studies, which tend to give higher heritability estimates, have estimates of up to 25%. Therefore, most of the variation we observe in the phenotype (right-handedness or left-handedness) is not explained by variation at the genetic level.  

This study tells us that, in addition to the common variation studied so far, rare genetic variation is also involved, but the observed effects are very small and therefore only detectable in such studies with very large samples.