Evaluating rare and common genetic variants and interaction with environment affecting mental diseases
Mental diseases, like schizophrenia, bipolar disorder and depression, rank the top causes of disability in the worldwide. Multigenerational cohort studies demonstrate heritability of risk of mental diseases, suggesting an important role for genetic variation. Better understanding of the genetic factors that predicate medication response will facilitate optimal clinical care tailored to individual patients. Since Genome-Wide Association Study (GWAS) hits only explain a small portion of disease variance by testing common variants, rare variants detected by whole-exome sequencing (WES), which are more deleterious and have larger effect sizes than their common counterparts. The UK Biobank has provided considerable resource of multidimensional data, including genetics (WES and GWAS), imaging data, environmental factors, and other markers for disease risk and clinical outcome after diagnosis. Depending on such immense resource, the main goal of this project is to identify associated genes with mental disease progression and prognosis by combining genetic data and electronic clinical records. Novel genes along with previously reported trait-specific common markers will then be further analyzed by combining imaging data. Next, genetic risk scores that can be used to help predict a person's risk of mental disorders and response to drug treatment when they are under other environmental conditions like eating habits, sleep quality, chronic conditions like cardiovascular diseases, autoimmune diseases, and aging-related diseases, infections and cancer.
We request to have full cohort of UK-Biobank data with detailed clinical (diagnoses, procedures, and medication use) and genotype data (GWAS and WES). Our findings may also provide genetic and gene-environment interaction (GxE) evidence for mental disease prevention and management. We expect to complete the proposed work within 36 months. However, this project may be extended beyond three years due to newly-released data which warrant extra validation of our findings.