Investigating the genetic and environmental relationship between left-handedness, mortality, disease and other life outcomes

Handedness refers to the preferential use of one hand over the other. Conversely, ambidexterity refers to the ability to perform the same action equally well with both hands. Hand preference is first observed during gestation as embryos begin to exhibit single arm movements. Across the life span, the consistent use of one hand leads to alterations in the macromorphology and micromorphology of bone, which results in enduring asymmetries in bone form and density. At the neurological level, handedness is associated with the lateralization of language (the side of the brain involved in language) and other cognitive effects. The prevalence of left-handedness in modern western cultures is approximately 9% and is greater in males than females. While handedness is conceptually simple, its aetiology and whether it is related to brain and visceral (internal organ) asymmetry is unclear.

Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we recently conducted the world’s largest genetic study of handedness in over 1.7 million individuals (Cuellar-Partida et al 2020). We found 41 genetic loci associated with left-handedness and 7 associated with ambidexterity (P < 5 × 10⁻⁸). We would now like to take this work forward and use this resource to investigate the relationship between handedness and a variety of life outcomes including mortality and common complex diseases. The successful candidate will gain experience across a wide range of advanced statistical genetics methodologies including Mendelian randomization (a way of using genetic variants to investigate putatively causal relationships), genome-wide association analysis (GWAS), genetic restricted maximum likelihood (G-REML) analysis of genome-wide data which can be used to partition variation in phenotypes into genetic and environmental sources of variation, genomic SEM, and instrumental variables analysis (using natural “experiments” to obtain information on causality from observational data).