Evaluating the Genetic Effects of Gut Microbiota on the Development of Neuroticism and General Happiness: A Polygenic...

Limited efforts have been invested in exploring the interaction effects between genetic factors and gut microbiota on neuroticism and general happiness. The polygenic risk scores (PRS) of gut microbiota were calculated from individual-level genotype data of the UK Biobank cohort. Linear regression models were then used to assess the associations between individual PRS of gut microbiota and mental traits and interaction analysis was performed by PLINK2.0. KOBAS-i was used to conduct gene ontology (GO) enrichment analysis of the identified genes. We observed suggestive significant associations between neuroticism and PRS for the genus Bifidobacterium (rank-normal transformation, RNT) (beta = -1.10, P = 4.16 × 10^-3) and the genus Desulfovibrio (RNT) (beta = 0.54, P = 7.46 × 10^-3). PRS for the genus Bifidobacterium (hurdle binary, HB) (beta = 1.99, P = 5.24 × 10^-3) and the genus Clostridium (RNT) (beta = 1.26, P = 9.27 × 10^-3) were found to be suggestive positively associated with general happiness. Interaction analysis identified several significant genes that interacted with gut microbiota, such as RORA (rs575949009, beta = -45.00, P = 1.82 × 10^-9) for neuroticism and ASTN2 (rs36005728, beta = 19.15, P = 3.37 × 10^-8) for general happiness. Our study results support the genetic effects of gut microbiota on the development of neuroticism and general happiness.