Investigating the Associations of Major Depressive Disorder with Various Health Outcomes in the Context of Common Genetic Variants: A Mendelian Randomisation Study

Abstract

Background: Depression is a leading cause of disability worldwide. The associations between major depressive disorder (MDD) and common health outcomes are well described but the biological mechanisms behind the associations of MDD with various health conditions are poorly understood. Methods: We investigated relationships between MDD and 16 mental and 17 physical traits using summary results of genome-wide association studies for these traits. Genetic correlations were analyzed using LD score regression and causal effects were analyzed using Mendelian randomization. Findings: MDD genetically correlates with a majority of the health-related traits and confers a causal effect on 10 mental traits (neuroticism, insomnia, schizophrenia, subjective well-being, bipolar disorder, autism spectrum disorder, attention deficit/hyperactivity disorder, anorexia nervosa, obsessive-compulsive disorder, and anxiety disorder) and four physical traits (cardiovascular disease, dyslipidemia, asthma, and osteoarthritis). Conversely, major depressive disorder is causally influenced by seven mental traits (neuroticism, insomnia, schizophrenia, subjective well-being, bipolar disorder, autism spectrum disorder, and attention deficit/hyperactivity disorder) and cardiovascular disease. Some key genes may contribute to the relationships of MDD with insomnia and cardiovascular disease. Interpretation: Genetic variation may underline the associations of major depressive disorder with various health outcomes. The study supports a causal role for genetic liability of major depressive disorder on most mental disorders and some physical conditions. Funding Statement: This work was supported by the National Natural Science Foundation of China No 81471364 (to FZ). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Not required.