Investigating schizophrenia as a complex multifactorial disorder
Schizophrenia has a complex aetiology involving both genetic and environmental factors. In this thesis, I describe my research into maternal malnutrition as a potential environmental risk factor and three candidate genetic risk factors for schizophrenia. I examined maternal malnutrition as a potential environment risk factor to schizophrenia in a large cohort dataset collected from a population in China (Wuhu region, Anhui Province) exposed to famine in 1960-1961. Our study shows that prenatal exposure to famine appears to approximately double the risk of schizophrenia, and has no significant effect on the rate of positive family history. Gene-environment interaction is proposed as a possible mechanism. I also carried out DNA association studies on a large Scottish case control sample set to investigate association between three candidate genes, namely DTNBP1, RGS4 and DISC1, and schizophrenia. Despite some modestly significant results from DTNBP1 and RGS4, our results essentially failed to replicate the initial reports. By contrast, DISC1 study showed significant association with schizophrenia for two markers in 5' end of the gene at allele, genotype and haplotype levels. The significant distributions of risk allele and haplotype are similar to the results from an earlier Finnish study.