Association Analysis Between Genetic Variations And Psychiatric Disorders

Schizophrenia, bipolar disorder and major depressive disorder are three common psychiatric disorders that affect about a lot of the population with lifelong devastating consequences. As typical complex diseases affected by environment and genetic factors mutually, genetic factors account about 73–90% for the onset of schizophrenia, 62~80% for bipolar disorder, about 37% for major depressive disorder. In the recent years, SNPs are usually chosen as markers in genetic researches on complex diseases. As the develop -ment of high-throughput arrays, there is a surge of genome-wide association study on these complex diseases.N-methyl-D-aspartate (NMDA) receptors, an ionotropic subtype of glutamate receptors, have been proposed as mediators of many common neuropsychiatric phenotypes including cognition, psychosis, and degeneration. GRIN2B encodes the NR2 subunit of NMDA receptors. Dystrobrevin binding protein 1 gene (DTNBP1) express in all principal neuronal populations of the hippocampus; the protein is located in presynaptic axon terminals of the glutamatergic neurons. In the first part we genotyped three SNPs of GRIN2B and DTNBP1 respectively in a set of 480 bipolar disorder patients and 480 normal controls in the Chinese Han population. Our data supported GRIN2B as having a role in the etiology of bipolar disorder. However we failed to replicated the association between DTNBP1 and bipolar disorder. There were no significant allelic, genotypic or haplotypic differences between cases and controls.In the very recent years, many studies highlight that copy number variations are implicated in the aetiology of complex diseases. Several studies provide evidence that copy number variations are over-represented in cases than controls. Several loci are replicated to be associated with schizophrenia, autism and other neuropsychiatric disorders.In our work we screened copy number variations in 2131 Schizophrenia patients, 1317 major depressive disorder patients, 1448 bipolar disorder patients and 1728 normal controls in total by Affymetrix 500K/ SNP6.0 arrays and real-time PCR, and then validated by Multiplex Ligation-dependent Probe Amplification (MLPA). We confirmed that CNVs at 15q11 was significant associated with schizophrenia and major depressive disorder.In our work, we conclude that GRIN2B is a risk factor of bipolar disorder in the Chinese Han Population, and CNVs at 15q11.2 are shared risk factors in schizophrenia and major depressive disorder. In the very recent years, the remarkable advances in molecular technologies such as chips and next generation sequencing will shed new light on the genetics of psychiatry disorders and assist us to understand the genetic mechanism of these complex disorders.