The role of sex in genetic association studies of depression

Project Abstract Depression is the most common mental illness in the U.S. affecting nearly 40 million adults age 18 years and older. Women are more likely to be affected by depression than men. Depression has both genetic and environmental influences. Depression is a polygenic disorder (due to the combined effects of many genetic variants) and depression rates differ by sex. The relationship between genes and depression is complex and influenced by sex. Thus, understanding the shared genetic basis of sex-specific differences for depression has great potential to lead to new biological understanding of the etiology of depression in females compared to males and to promote the development of novel and more effective pharmacotherapies. The underlying goal of this proposal is to develop and evaluate methods to examine the role of sex in genetic association studies of depression. These methods will be applied to the UK Biobank. The UK Biobank is one of the largest biobanks available at present and represents an extensive resource with both genetic data and depression phenotypes (approximately 474,000 participants). The Mass General Brigham Biobank (approximately 33,000 participants) will be used for validation and assessment of the robustness of the approaches. The grant focuses on methods development applied to depression and the role of sex in genetic association studies of depression; however, our ultimate goal is to develop approaches that are applicable to a broad range of mental health and addiction phenotypes. We will also create publicly available software packages to implement these new approaches, so that they will be broadly accessible to the scientific community.