GENETICS OF SUBSTANCE DEPENDENCE: WHAT WE KNOW AND HOW WE KNOW IT

UNODC Scientific Consultation – December 2015

 GENETICS OF SUBSTANCE DEPENDENCE: WHAT WE KNOW AND HOW WE KNOW IT

Joel Gelernter Professor of Psychiatry, and Professor of Genetics and Neurobiology; and Director, Division of Human Genetics (Psychiatry) Yale University School of Medicine.

Risk for such substance dependence traits as alcohol, nicotine, and cannabis dependence, is influenced both by genes and by environment. Recent progress in complex trait genetics, engendered primarily by new technology and new statistical methods, has been unprecedented in the history of biology; most of this progress has occurred in the last ten years. As a result we now know specific risk alleles for many substance dependence traits. As risk genes have been revealed, we are learning of new pathophysiology, guided to biosystems and biological pathways by knowledge of risk alleles. Proteins encoded by genes may identify new pharmacological targets, and genetic variation at some loci predicts treatment response. Results for alcohol, nicotine, and cocaine dependence are discussed, including clinical implications and next steps.

About the author

Dr. Gelernter is Foundations Fund Professor of Psychiatry and Professor of Genetics and Neurobiology; and Director, Division of Human Genetics (Psychiatry), at Yale University School of Medicine. He studied music and biology as an undergraduate at Yale University; completed his MD at SUNY-Downstate; and trained in psychiatry at Western Psychiatric Institute and Clinic (Pittsburgh) and the NIMH. He returned to Yale in 1988 to join the psychiatry faculty.

The research focus of his laboratory is genetics of psychiatric illness. This includes a range of behavioral phenotypes including cocaine, opioid, nicotine, cannabis, methamphetamine, and alcohol dependence, posttraumatic stress disorder (PTSD), panic, and other anxiety disorders. In addition, they study a range of intermediate phenotypes, such as neuroimaging measures; and basic issues in population and complex trait genetics.

The overall approach involves study of genetic polymorphism and sequence variation, on a molecular level, and from the perspective of population genetics, with studies based in the US, and collaborations across the US and in Thailand and Taiwan. Dr. Gelernter also co-leads the Substance Use Disorders section of the Psychiatric Genomics Consortium.

Dr. Gelernter’s laboratory has published the first genomewide association studies (GWAS) for cocaine and opioid dependence, and pioneering GWAS studies of PTSD, alcohol dependence, and related phenotypes. All of these studies have resulted in the identification of novel risk loci. Whole-genome and whole-exome sequence studies of substance dependence traits are in progress.