Study Of Genetic And Neural Substrates Of Personality

Objective:Personality is the specific pattern characterizing the individual’s thinking,feeling,and behavior.Since personality is closely related to physical and mental health outcomes,exploring the genetic and neural mechanisms of personality is of great significance for human’s well-being.Personality is shaped both by genetic and environmental factors and shows differences across cultures and geographic regions.Although there are genome-wide association studies(GWAS)of personality based on large European samples,no GWAS has been carried out in large-sample Chinese Han population.Here we aim to identify the genetic variants and genes related to personality evaluated by NEO-FFI(Neuroticism–Extraversion–Openness Five-Factor Inventory),including agreeableness,conscientiousness,extraversion,neuroticism and openness,and to further disclose the molecular biological mechanism through which these variants and genes affect personality.Then,by using multiple environmental variables and multi-mode brain imaging data,we aim to disclose the pathway that environmental variables modulate personality under the mediation of brain structure and function.Methods:In the first part,we performed the GWAS and genome-wide gene association study(GWGAS)of personality in 4895 healthy Chinese Han participants aged 18-30 years to identify the significant SNP(single nucleotide polymorphisims)and genes,and we also evaluated the SNP-based heritability and compared with the results from European GWAS meta-analysis.In the second part,we first established the relationship between multiple environmental variables and each dimension of personality using sparse canonical correlation analysis and obtained the environmental canonical variable(a linear combination of the multiple environmental variables).Then,by using multiple regression analysis,we identified brain regions whose structure or function are correlated with personality.Finally,mediation analysis was applied to identify the environmental canonical variable-brain structure and function-personality pathways.Results:In the first part,we identified a genome-wide significant locus related to agreeableness locating at the intron of LAMA2,at the sixth chromosome,including two independent SNPs,rs12209058 and rs140944404.Many SNPs in linkage disequilibrium with these two SNPs could regulate gene expression of LAMA2.We also found that SNPs in the intron of LAMA2 were related to smoking status and educational attainment.The heritability(h~2)of agreeableness and openness was about0.15,close to those estimated in European cohorts.In the second part,we found that all five dimensions of personality were related to multiple environments such as family economic status,parenting,social support,adverse childhood experience,mobile phone using and etc.The openness was mainly correlated with social-economic status such as family income and parents’education.Besides,we found that the openness was negatively related to gray matter volume and ALFF(amplitude of Low Frequency Fluctuation)of bilateral medial superior frontal gyrus,as well as FA(fractional anisotropy)of the corpus callosum.Most importantly,we found a significant indirect effect suggesting that the gray matter volume,ALFF of bilateral medial superior frontal gyrus and FA of the corpus callosum may mediate the association between environmental canonical variable and openness.Conclusion:Our study found that SNPs in the intron of LAMA2 may play a role in agreeableness through regulating the gene expression of LAMA2.The SNP heritability of agreeableness and openness were lower than the heritability estimated in twins and family analysis which indicates that the genetic architecture of personality is highly complex.Also,our study not only identified a high correlation between multiple environments(such as social-economic status,parenting,social support,adverse childhood experience,mobile phone using and etc)and personality,but also shed light on the neural basis of openness that the structure and function of the bilateral medial superior frontal gyrus and the white matter integrity of the corpus callosum might mediate the association between multiple environmental variables and openness.