Causal effects of childhood obesity on neuroticism and subjective well-being: A two-sample Mendelian randomization study

Abstract

BackgroundChildhood obesity is linked to both neuroticism and subjective wellbeing (SWB); however, the causal relations between them remain unclear. MethodsTwo-sample Mendelian randomization (MR) analysis was applied to determine the causal effects of childhood BMI (n = 39,620) on neuroticism (n = 366,301) and SWB (n = 298,420) using summary statistics from large scale genome-wide association studies (GWASs). Inverse-variance weighting (IVW), weighted mode, weighted median, and MR-Egger approaches were used to estimate the causal effects. Sensitivity analyses including the Cochran's Q statistics, MR-Egger intercept test, MR-PRESSO global test, and the leave-one-out (LOO) analysis were used to assess potential heterogeneity and horizontal pleiotropy. Two-step MR mediation analysis was employed to explore the potential mediation effects of neuroticism on the causal relationship between childhood BMI and SWB. ResultsOur study revealed that genetically predicted higher childhood BMI was causally associated with increased neuroticism (beta = 0.045, 95%CI = 0.013,0.077, p = 6.066e-03) and reduced SWB (beta = −0.059, 95%CI = -0.093,-0.024, p = 9.585e-04). Sensitivity analyses didn't detect any significant heterogeneity and horizontal pleiotropy (all p > 0.05). Additionally, the two-step MR mediation analysis indicated that the causal relationship between childhood BMI and SWB was partially mediated by neuroticism (proportion of mediation effects in total effects: 21.3 %, 95%CI: 5.4 % to 37.2, p = 0.0088). ConclusionGenetically proxy for higher childhood BMI was associated with increased neuroticism and reduced SWB. Further studies were warranted to investigate the underlying molecular mechanisms and potential use of weight management for improving personality and SWB.