Analyses Of Shared Genetic Variants Between Personality And Subjective Well-being And Association Study Of Neuroticism-related Genes

Personality is a unique and relatively stable pattern of thinking,emotional attitude and behavior pattern in one’s life.Subjective well-being(SWB)is an overall emotional and cognitive evaluation of people’s life,including well-being,achievement and life satisfaction.Personality is one of the strongest and most stable predictors of SWB;both personality and subjective well-being show a certain degree of heritability.Previous studies have revealed a strong correlation between personality traits and SWB,but the underlying biological mechanism,especially the specific functional genes or gene locus,have not,to the best of our knowledge,been explored.In addition,neuroticism as one important personality trait,usually presents negative emotions such as high pressure,anxiety,irritability and emotional instability,which are highly related to major depressive disorder,schizophrenia and other mental diseases.Thus a more thorough study on neuroticism will shed light on new ideas for better understanding of such mental disorders.This dissertation is composed of two parts as follows.The first part of this dissertation is to verify whether there is a correlation between personality traits and subjective well-being and try to find the common genetic variants between them,from the genetic perspective.The subjects in this study included 890 undergraduates from Shandong,China.The main method was scale evaluation:the Big Five Inventory was adopted to evaluate their personality traits and SWB was reflected by the score of Satisfaction with Life Scale.Five single nucleotide polymorphisms(SNP)(rs1426371,rs2164273,rs322931,rs3756290,rs490647)were selected from previous literature and genotyped for genetic association study.The results showed that neuroticism was negatively correlated with SWB,while extraversion,agreeableness,responsibility and openness were positively correlated with SWB.Three SNPs(rs2164273,rs3756290,rs490647)out of the five-SNP penal were observed to be statistically correlated with personality.Among them,rs490647,which is located downstream of GRIK3 gene,was also found related to SWB.Individuals with G/G genotype at this locus were more likely to be extraverted,open and more satisfied with their life.As a result,they were less likely to demonstrate neurotic personality traits.Our study suggested that rs490647 may serve as a good genetic predictor for personality and subjective well-being.The second part is the gene association study of neuroticism,which is closely related to mental illness in personality traits.The subjects in this study included 727 undergraduates from Shandong,China.We evaluated neuroticism using participant’s score on an 8-item of the neuroticism scale from the Big Five Inventory.Five SNPs(rs1557341,rs12903563,rs12938775,rs2150426,rs2572431)were selected from the literature and genotyped for genetic association study.Only rs 1557341 of CELF4 showed remarkable genetic association with neuroticism;this variant was also correlated with extraversion,conscientiousness and openness to experience.Individuals with T/T genotype at this site tend to have lower levels of neuroticism and greater chance to be extraverted,conscientious and open.In summary,identification of CELF4 locus rs1557341 offers a new lead on better comprehending the neurobiological mechanism of neuroticism and mental disorders.