Yunnan Han The Genetic Polymorphism Of CRHBP Associated With Schizophrenia And Aggressive Behavior

Objective:To assesss the genetic relationship between4polymorphic loci of CRHBP and schizophrenia, aggressive behavior in Yunnan Han population, to provide a scientific theory basis for the prevention, diagnosis, personalized treatment of schizophrenia and the legal capacity evaluation of patients with schizophrenia. CRHBP is a gene in HPA axis which influences the morbidity of schizophrenia, the incidence of aggressive behavior.Methods:The genotype and allele frequencies of the4Tag SNPs in168Yunnan Han patients with schizophrenia and correspondingly363healthy individuals were detected using iMLDR. Perform statistical analyses using software like SPSS19.0, Haploview4.2, PHASE2.1and MDR2.0.Results:1. The analysis results of epidemiologyThe average age of patients with schizophrenia was49.56±12.078years old, average initial age was30.421±1.567years old, male patients with earlier age than female (P<0.05), average duration was19.78±12.110years. Group of female was at higher risk for schizophrenia than males (P<0.05, OR>1), but males with more aggressive behavior (P<0.05, OR>1). The groups of low levels in education with junior middle school or below, unmarried or divorced, unemployed, farmers or workers, smoking, drinking, et al, were high-risk groups of schizophrenia and aggressive behavior (OR>1).2. The result of single locus analysisThe distributions of genotypes and alleles in4loci had no significant difference in healthy controls and patients with schizophrenia (P>0.05), and there were no gender differences yet. The distributions of genotypes and alleles in rs32897and rs7718461were associated with physical aggression and verbal aggression (P<0.05), and there were gender differences. The distributions of genotypes in rs10062367were associated with physical aggression in male patients (P=0.027). There was no correlation with statistical significance between the polymorphism of single loci rs7721799and three types of aggressive behavior (P>0.05).3. The result of linkage disequilibrium analysisThere were strong linkage disequilibrium between rs10062367and rs7721799, rs7718461(D’>0.8). In healthy controls and patients with schizophrenia, there were different linkage disequilibrium between rs7721799and rs32897, rs10062367. In schizophrenia patients without and with aggressive behavior, there were different linkage disequilibrium between rs7718461and rs7721799, rs10062367.4. The result of haplotype analysisHaplotype ACGG、GCGA may be the risk factors of schizophrenia (P<0.05), GCAG may be its protective factor (P<0.05), the distributions of three haplotypes were different in males and females. Haplotype GTGG and ATGG, ATAG, GCGG can respectively increase the risk of verbal aggression, property aggression, physical aggression (P<0.05), while GTAG and GTGA can reduce the risk of verbal aggression (P<0.05), there were differentce with the distributions of haplotypes in males and females. Haplotype GCGA may be the risk factor in patients with physical aggression (P<0.05), the distribution had no statistical significance in males and females.5. The result of loci-loci interaction analysisThere was no model with statistical significance of loci-loci interaction analysis in healthy controls and patients with schizophrenia, patients without or with verbal aggression and property aggression (P>0.05), but the model rs7721799-rs32897-rs10062367was significantly associated with physical aggression in patients (P=0.011).Conclusion:There was no significant correlation between the polymorphism of single locus, loci-loci interaction model of rs7721799, rs32897, rs7718461, rs10062367in CRHBP and schizophrenia in Yunnan Han population, but haplotypes can influence the risk of schizophrenia, and the distributions of part of haplotypes were different in females and males. There was significant correlation between the polymorphism of single locus in3loci apart from rs7721799and aggressive behavior, different types of aggression with different significantly associated haplotypes, and those distributions had differences in females and males. The mode rs7721799-rs32897-rs10062367was asscosiated with physical aggression in patients, but there was no model with statistical significance in other groups. There were strong linkage disequilibrium between rs10062367and rs7721799, rs7718461.