Association Analysis Between Common Mutations Of HCN1 Gene And Schizophrenia In The Chinese Uygur Population

Background: Schizophrenia is a complex chronic brain disorder with a lifetime prevalence of ~?0.5%–1% across all human populations.The detailed cause of schizophrenia is unclear,the treatment is largely symptom-specific and lacks precision.In recent years,the advancement of complex disease genomics research,more and more studies on susceptibility genes of schizophrenia have been carried out,and thousands of risk loci have been identified in different populations.However,due to the genetic heterogeneity of complex diseases,risk-genotype frequency at loci showing associations might differ substantially among different populations.Recently,two large-scale GWAS studies have found many new sites associated with schizophrenia,and found that HCN1 was a new risk gene for schizophrenia in the European population.The full name of HCN1 is a hyperpolarized activated cyclic nucleotide-gated potassium channel 1,which has a voltage regulation effect.It is abundantly expressed in the hippocampus of the brain,and is also associated with neurotransmitters release and synaptic excitability.However,the Chinese Uygur population is a mixture of Chinese Han and Western European populations,it is unclear whether HCN1 is also associated with schizophrenia in this population.Objective: Most of the previous studies were in European population and found that HCN1 is associated with schizophrenia.It is unclear that the relationship between HCN1 and disease in the Chinese Uygur population.Therefore,this study attempt to explore whether HCN1 common variant is a risk factor for schizophrenia in this population.Methods: This study included 985 schizophrenia patients and 1218 healthy controls recruited from the Chinese Uygur population.We selected five tag SNPs(rs12519313,rs10060015,rs16902112,rs16902197 and rs12659024)via Haploview software,and they were genotyped by the Massarray nucleic acid typing system.Finally,the genotyping results of the two groups of five loci were analyzed.Furthermore,we also analyzed whether the two imputed SNPS rs1501357,rs9292918 were risk genes for schizophrenia in the Chinese Uygur population by linkage disequilibrium test.Results: The Hardy-Weinberg equilibrium results showed that the P value of rs16902112 was less than 0.05,so rs16902112 did not follow the genetic equilibrium and was abandoned in the following studies.The P values of the remaining four sites results were all greater than 0.05.There was no significant differences between the patients and controls.Among them,the P values of rs12519313 allele frequency was 0.834 and genotype frequency was 0.806,which was not a risk locus.The allele and genotype frequencies of rs10060015 were 0.889 and 0.539.The results show that the P value was greater than 0.05.The allele and genotype frequencies of rs16902197 were similar,with P values of 0.288 and 0.325.The allele and genotype frequencies of rs12659024 were 0.185 and 0.104 in the two groups.Compared with the other sites,the frequency of rs12659024 locus was close to 0.05.The locus may have significance for further studies.In order to validate the reliability of results,we conducted a gender analysis of the subjects,and the results showed that the male and female groups were not associated with schizophrenia.In addition,we also conducted a subgroup analysis of positive and negative symptoms.The statistics showed that the four sites on HCN1 were not associated with positive or negative symptoms of schizophrenia.The results of linkage disequilibrium test indicated that there was a strong linkage disequilibrium between the five loci.In addition,there is a linkage disequilibrium between the two imputed SNPs and rs16902112,rs10060015 locus in this study.Therefore,there is no correlation between the two imputed locus and schizophrenia.Conclusions: Our study showed that the common variation of the HCN1 gene in the Chinese Uygur population was not significantly associated with schizophrenia.However,our research further enriched the genetic association studies of schizophrenia in different populations,and provided valuable information for the subsequent study of GWAS in the Chinese Uygur population.