Poster Presentation GENEMAPPERS 2024

Investigating associations between early-life environmental factors and handedness using multivariable regression and proxy gene-by-environment Mendelian randomization (#87)

Daisy Crick 1 , Sarah Medland 2 , George Davey-smith 3 , David Evans 1
  1. University of Queensland, St Lucia, QLD, Australia
  2. QIMR Berghofer Research Institute, Brisbane, QLD, Australia
  3. Integrative Epidemiology Unit, University of Bristol, Bristol, England

Although a genetic component to hand preference has been confirmed, most variation in handedness appears to be driven by environmental factors [1]. Previous observational epidemiological studies have aimed to identify environmental factors that causally influence handedness [2], but as with many observational studies, confounding and bias can produce spurious associations.

Using data from the UK Biobank (UKB), we investigated potential causes of handedness and specifically the effects of maternal smoking during pregnancy. We ran multivariable regression analyses and found that, when controlling for potential confounders, being male (OR: 1.27; CI: 1.24, 1.31) and being part of a multiple birth (OR: 1.16; CI: 1.06, 1.26) increased the likelihood of being left-handed, while being breastfed increased the likelihood of being right-handed (OR: 0.89; CI: 0.85, 0.91). We also found that maternal smoking during pregnancy increased the probability of being right-handed in offspring after adjustment for confounders (OR: 0.95; CI: 0.91, 0.98).

 We then investigated the relationship between maternal smoking during pregnancy and offspring handedness using a proxy gene-by-environment Mendelian randomization study design [3]. UKB participants’ own genotype for smoking heaviness (according to the variant rs16969968 in the CHRNA5 gene) was used to proxy the genotype of their mothers at the same locus, and therefore their mother’s smoking behaviour. We then stratified the sample based on reported maternal smoking status during pregnancy since any causal effect of maternal smoking on handedness should only be observed in individuals whose mothers smoked when pregnant. We found little evidence for an effect of maternal smoking during pregnancy on offspring hand preference in mothers that smoked (OR: 0.98; CI: 0.95, 1.02).

Our findings highlight that while there have been promising leads in understanding the determinants of handedness, the majority of environmental factors contributing to variation in the trait are yet to be resolved.

  1. 1. Cuellar-Partida, G., et al., Genome-wide association study identifies 48 common genetic variants associated with handedness. Nature Human Behaviour, 2021. 5(1): p. 59-70.
  2. 2. de Kovel, C.G.F., A. Carrión-Castillo, and C. Francks, A large-scale population study of early life factors influencing left-handedness. Scientific Reports, 2019. 9(1): p. 584.
  3. 3. Yang, Q., L.A.C. Millard, and G. Davey Smith, Proxy gene-by-environment Mendelian randomization study confirms a causal effect of maternal smoking on offspring birthweight, but little evidence of long-term influences on offspring health. International Journal of Epidemiology, 2019. 49(4): p. 1207-1218.