Association for Behavior Analysis International

For years, the field of psychiatric genetics has focused on disease diagnoses; however, “our genes don’t seem to have read the DSM.”Instead, we have been encouraged to study basic dimensions of functioning (aka Research Domain Criteria, intermediate phenotypes or endophenotypes) using non-disease phenotypes in large population-based cohorts. Using this approach, we have now piled on hundreds of novel genetic loci associated with multiple complex phenotypes, which have been further utilized to elucidate the genetic basis of psychiatric diseases. The purpose of this talk is to review the use of non-disease phenotypes to elucidate and decompose psychiatric diseases. Impulsivity, which has been defined as “actions which are poorly conceived, prematurely expressed, unduly risky or inappropriate to the situation, and that often result is undesirable consequences” (Daruna and Barnes 1993) is an endophenotype for a constellation of psychiatric diseases, including ADHD and substance use disorders (SUD). Dr. Sanchez-Roigewill present a series of studies to dissect the genetics of several forms of impulsive personality traits. This work will reveal strong genetic correlations between multiple measures of impulsivity and risk tolerance, and both ADHD and smoking and other SUD-related traits. Another examples of success come from the genetics of other non-disease phenotypes, namely the Alcohol Use Disorder Identification Test, as proxies for alcohol use disorders. Dr. Sanchez-Roige will present a multivariate genome-wide association study of AUDIT phenotypes. This approach will uncover novel genetic effects which might have been obscured in traditional GWAS. This work will also demonstrate how a non-clinical phenotype, such as AUDIT, which has demonstrated to share a common genetic basis with alcohol use disorders but can be measured in much larger sample sizes, could serve as a complementary alternative to traditional ascertainment strategies for genetic studies. Lastly, Dr. Sanchez-Roige will close the talk by presenting a novel strategy to examine the multivariate genetic architecture of complex traits and diseases from the Externalizing Consortium – a collaborative effort that capitalizes on several large-scale GWAS with the goals of (a) estimating genetic correlations across externalizing phenotypes, which are associated with a constellation of co-morbid disorders and behaviors that are characterized by deficits in impulsive action, (b) identifying genes involved in a shared underlying liability to externalizing psychopathology versus genes that are unique to specific outcomes, and (c) increasing the predictive ability of polygenic scores for externalizing phenotypes and psychiatric, health and social outcomes.

Members interested in the biology (genetics, neuroscience, behavior) of psychiatric disorders, particularly substance use disorders, and related phenotypes, such as impulsivity.