Study 36 – Genetic Dissection in Pedigrees of Substance Use and Mood Disorders Comorbidity

Investigators: Henriette Raventós, Nelson B. Freimer, and Victor Reus

Release Date: TBA

Abstract: Substance use disorders (SUDs) and mood disorders (MDs) are highly prevalent disorders that, on their own, result in devastating outcomes and burden on individuals, their families, and society as a whole. Their comorbidity, however, complicates treatment and aggravates outcomes. While both types of disorders are heritable, the nature of their shared genetic susceptibility remains unclear. An increased understanding of the factors behind this comorbidity could lead to an expanded capability for prevention and/or treatment. This study will collect pilot data for a project which aims to increase the probability of identifying genetic variants contributing to SUD/MD comorbidity, by investigating families from a genetic isolate in the Central Valley of Costa Rica (CR) including many members diagnosed with severe bipolar disorder (BP-I). This genetic isolate resulted from recent expansion of an extreme bottleneck, and has been studied in an existing project (R01MH075007) that focused on identifying genetic variants contributing to BP-I and BP-I endophenotypes. We will leverage samples and phenotypic, genotypic and whole genome sequence data from ~450 members of these pedigrees from the existing project. We will execute a systematic phenotyping procedure for SUD and potential SUD-endophenotypes and record the phenotype distribution in up to 100 individuals assessed in our existing project and an additional 50 unstudied participants with an SUD diagnosis, who are first-degree relatives of our existing subjects. Based on preliminary analyses of SUD/MD comorbidity and of the heritability of SUD endophenotypes, we will further investigate the genetics behind SUD/MD comorbidity in larger-scale and longer-term studies in CR and in pedigrees from a similar genetic isolate in Antioquia, Colombia.