Gene-based association analysis identifies 190 genes affecting neuroticism

Abstract Neuroticism is a personality trait, which an important risk factor for psychiatric disorders. Recent genome-wide studies reported about 600 genes potentially influencing neuroticism. Little known the mechanisms of their action. Here, we aimed to conduct more detailed analysis that can regulate level Using UK Biobank-based GWAS summary statistics, performed gene-based association using four sets within-gene variants, each set possessing specific protein-coding properties. To guard against influence strong signals outside gene, used specially designed procedure called “polygene pruning”. As result, identified 190 associated with neuroticism due effect variants rather than gene. Thirty eight these are new. Within all identified, distinguished two slightly overlapping groups obtained from and non-coding variants. Many in former group included pathogenic For some latter group, found evidence pleiotropy gene expression. bioinformatics analysis, prioritized showed contribute through most appropriate candidate genes.