Genome–wide association study for risk taking propensity indicates shared pathways with body mass index

Abstract

Risk-taking propensity is a trait of significant public health relevance but few specific genetic factors are known. Here we perform a genome-wide association study of self-reported risk-taking propensity among 436,236 white European UK Biobank study participants. We identify genome-wide associations at 26 loci ( P < 5 × 10 ⁻⁸), 24 of which are novel, implicating genes enriched in the GABA and GABA receptor pathways. Modelling the relationship between risk-taking propensity and body mass index (BMI) using Mendelian randomisation shows a positive association (0.25 approximate SDs of BMI (SE: 0.06); P = 6.7 × 10 ⁻⁵). The impact of individual SNPs is heterogeneous, indicating a complex relationship arising from multiple shared pathways. We identify positive genetic correlations between risk-taking and waist-hip ratio, childhood obesity, ever smoking, attention-deficit hyperactivity disorder, bipolar disorder and schizophrenia, alongside a negative correlation with women’s age at first birth. These findings highlight that behavioural pathways involved in risk-taking propensity may play a role in obesity, smoking and psychiatric disorders.

Abstract

Emma Clifton et al. report a genome-wide association study of risk taking propensity amongst UK Biobank participants. They identify 26 loci, 24 of which are novel, and use Mendelian randomisation analysis to explore the relationship between risk-taking propensity and BMI.