Genetic Susceptibility Study Onpsychiatric Disorders Based Onlarge‐Scale Sample

Schizophrenia, major depression and bipolar disorder are three majorpsychiatric disorders. Schizophrenia is a severe mental disease affecting about1%ofthe world population. Major depression affects3^-5%of males and8-10%of femaleswithin a year-long period in North America and is considered to be moderatelyheritable. Bipolar disorder is also a severe illness with a prevalence of about2.2%foradults in the USA. Although the real causes of the above diseases are still unclear,genetic factor is considered to be an important component in each disease's etiology.Recently, in a genome-wide association study (GWAS) and a follow-upinvolving7,676schizophrenic cases and29,057normal controls recruited fromCaucasian population, Stefansson et al. reported7common SNPs which weresignificantly associated with schizophrenia. To investigate whether these risk lociwere significant in Chinese Han population, we analyzed the7SNPs in2,496schizophrenia patients and5,184normal controls in the first part of this thesis. Wefound only3of the7SNPs were frequent in Chinese Han population. Therefore, weadditionally genotyped2common SNPs in the risk region/gene. Finally, rs6932590(p=0.00096), rs3131296(p=1.29×10^-6) and rs3130375(p=1.76×10^-5) in majorhistocompatibility complex (MHC) region and in TCF4gene were significant in oursample set. A meta-analysis considering published GWAS results were alsodemonstrated.Our results confirmed that common risk factors in the MHC region andTCF4gene were associated with schizophrenia in Chinese Han population, but we didnot replicate an association for NRGN gene (rs12807809).In the second part of this thesis, we focused on the FoxP2gene. FoxP2gene,located on7q31, encodes a transcription factor. It was first discovered throughinvestigations of a large multigenerational family (the KE family) with a rare severespeech and language disorder. Subsequent studies gave powerful and convincingfunctional evidence to the connection between FoxP2and language disorder.Language disorder is commonly considered as a core symptom of schizophrenia and some other mental diseases; thus, we decided to investigate whether FoxP2geneplayed a significant role in schizophrenia, major depression or bipolar disorder in asample set recruited from Chinese Han population. In this study, we focused on12SNPs in FoxP2gene and carried out case-control studies in1135schizophreniapatients,1135unrelated major depression patients,1135unrelated bipolar disorderpatients and1135unrelated normal controls recruited from Chinese Han population.We found rs10447760was significantly associated with schizophrenia (allelicp=0.00069) and major depression (allelic p=0.0011). Our study indicated that the rarevariant rs10447760in FoxP2may play an important role in schizophrenia, majordepression in Chinese Han population.