47th Annual Convention; Online; 2021
All times listed are Eastern time (GMT-4 at the time of the convention in May).
|The Use of Endophenotypes to Further Our Understanding of Psychiatric Genetics|
|Monday, May 31, 2021|
|12:00 PM–12:50 PM |
|Area: SCI; Domain: Applied Research|
|Chair: Suzanne H. Mitchell (Oregon Health & Science University)|
|CE Instructor: Suzanne H. Mitchell, Ph.D.|
|Presenting Author: SANDRA SANCHEZ-ROIGE (University of California, San Diego; Vanderbilt University Medical Center)|
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.
|Instruction Level: Intermediate|
|Target Audience: |
Members interested in the biology (genetics, neuroscience, behavior) of psychiatric disorders, particularly substance use disorders, and related phenotypes, such as impulsivity.
|Learning Objectives: At the conclusion of the presentation, participants will be able to: (1) discuss how population-based cohorts like 23andMe and UKB have revolutionized our understanding of complex traits; (2) describe how the use of sophisticated phenotypes like the Alcohol Use Disorder Identification Test can dissect aspects of drug use and misuse and can be inexpensively measured in large cohorts; (3) describe the use of intermediate phenotypes to enable translational research.|
|SANDRA SANCHEZ-ROIGE (University of California, San Diego; Vanderbilt University Medical Center)|
|My work is focused on understanding causal factors contributing to drug addiction and diseases characterized by high levels of impulsivity. In the past, I used behavioral and pharmacological experiments and molecular analysis to address this question, with special emphasis on translational validity to human studies. I identified that high impulsivity was both a cause and a consequence of human and mouse alcohol binge drinking. My current research focuses on the quantitative analysis of complex traits in humans, and translating some of our research findings in mouse and rat models. In particular, I have identified genes in humans that are associated with impulsivity and I am now producing mutant mice to dissect the molecular events associated with high impulsivity. In parallel, my newly formed laboratory uses genetic tools to unravel the biology of substance use disorders and comorbid psychopathology. I use big data and high-throughput phenotyping to identify individuals with substance use disorders phenotyped by using electronic health records, leveraging access to one of the largest biobanks in the US, BioVU. The ultimate goal of future work is to study the etiology of a range of psychiatric disorders characterized to varying degrees by excessive impulsive behavior, including drug addiction and ADHD.|
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