Vignesh Rajagopalan

Heritability of Psychiatric Disorders and their Genetic Correlation with Cardiovascular Disease Risk Factors

Started July 29, 2023

Abstract or project description

Psychiatric disorders are a leading cause of disability and mortality worldwide. Such disorders are influenced by genetic variants that act in conjunction with environmental factors. There is evidence that patients with Coronary Artery Disease (CAD) are at a high risk to develop Major Depressive Disorder (MDD). There is a dire need to understand the underlying genetic relationships among psychiatric disorders and Cardiovascular disease risk factors. The aim of this project was to compare two statistical regression techniques, LDSC and HDL on GWAS datasets to estimate heritability (genetic influence) of the above disorders/traits and evaluate genetic correlation among them. This data was used for gene pathway analysis of the mapped genes. The Psychiatric disorders considered were Major Depressive Disorder (MDD), Bipolar Disorder (BiP), Schizophrenia (ScZ) and major CVD risk factors were Coronary Artery Disease(CAD), Type-2 diabetes. The results from LDSC and HDL showed that all three psychiatric disorders were highly heritable(0.5-0.75) and highly genetically correlated (0.3-0.74). MDD showed moderate correlation with CAD (0.29) and Diabetes (0.18). HDL showed more precise estimations for genetic correlation with 40% lower standard error than LDSC. The gene pathway analysis showed that the genes involved in MDD, CAD and Diabetes are enriched for the following pathways: Immune system, Developmental Biology, Metabolism, Signal Transduction, Neuronal System, Cellular responses to stimuli and Metabolism of proteins. Statistical genetics and gene pathway analysis can give us insights into complex genetic relationships among diseases/traits. Future genetic research will lead us to better diagnostic accuracy and precision medicine discovery.