Recent Advances in Handedness Genetics

Abstract

Around the world, about 10% people prefer using their left-hand. What leads to this fixed proportion across populations and what determines left versus right preference at an individual level is far from being established. Genetic studies are a tool to answer these questions. Analysis in twins and family show that about 25% of handedness variance is due to genetics. In spite of very large cohorts, only a small fraction of this genetic component can be pinpoint to specific genes. Some of the genetic associations identified so far provide evidence for shared biology contributing to both handedness and cerebral asymmetries. In addition, they demonstrate that handedness is a highly polygenic trait. Typically, handedness is measured as the preferred hand for writing. This is a very convenient measure, especially to reach large sample sizes, but quantitative measures might capture different handedness dimensions and be better suited for genetic analyses. This paper reviews the latest findings from molecular genetic studies as well as the implications of using different ways of assessing handedness.

Quantitative multidimensional phenotypes improve genetic analysis of laterality traits

“…Parent-offspring regression in ALSPAC also showed significant heritability for handedness and footedness when using the quantitative phenotypes. We conclude that the quantitative phenotypes are better suited to capture the polygenic nature of handedness as expected under a liability threshold model [ 67 ]. The lack of association between the PRS derived from a recent large-scale GWAS for categorical handedness [ 24 ] suggests the influence of separate genetic factors.…”

Insights Into Human and Nonhuman Primate Handedness From Measuring Both Hands

“…The answer to this provocative question remains elusive. Genetic explanations, including those arising from genomewide association studies, although traditionally popular in handedness research, have not revealed any compelling answer to this question (Cuellar-Partida et al, 2021; de Kovel & Francks, 2019; Paracchini, 2021).…”

Light-induced asymmetries in embryonic retinal gene expression are mediated by the vascular system and extracellular matrix

“…Moreover, additive genetic factors explain only one quarter of the variance in human handedness, and it has been suggested that nonshared environmental factors can explain part of the remaining variance 20 , 115 (but see Refs. 116 – 118 ). Hence, to understand the ontogeny of functional and brain lateralization we must elucidate the interaction between endogenous and environmental factors 2 , 3 , 11 , 14 , 17 , 66 , 67 , 69 – 71 .…”