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Whole Genome Sequencing In Multiplex Families

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Brien Riley, Ph.D. is Associate Professor in the Department of Psychiatry. He is a molecular geneticist interested in identifying genes that contribute to variation in the brain, central nervous system function, and psychiatric illness risk and behavior. These interests developed after he completed his bachelor’s degree in psychology, as a result of his dissatisfaction with the field’s way of approaching brain function and dysfunction. He was frustrated “because the field of psychology did not, and mostly still does not, really address the complex function of the brain itself, preferring to work in abstract constructs that hopefully represent those underlying functions.”

Although Dr. Riley then worked in a rodent stress biology and behavior lab for two years after graduation, he subsequently took several years off from science. When he returned to science, he started working at St. Mary’s Hospital Medical School on a molecular genetics project in the early days of gene mapping for linkage studies. His boss at the time had wanted him to stay and do a PhD in molecular genetics, but Dr. Riley was torn between genetics and international development. However, his boss ultimately figured out how to combine his interests in Africa, genetics, and mental illness into a project on the genetics of schizophrenia in the Bantu population of southern Africa. In November of 1993, he traveled to Johannesburg, where he collected samples from families in Soweto, launching his career in molecular genetics. He has been focused on the molecular genetics of mental illness ever since.

Currently, Dr. Riley’s lab focuses primarily on the genetics and genomics of schizophrenia and alcohol/substance use disorders, and is also involved in studies of major depression and autism. His lab’s work on schizophrenia is currently focused on whole genome sequencing in multiplex families from the homogeneous population of Ireland. This study seeks to exploit the elevated recurrence risk in multiplex families compared to singleton cases. We detect no elevation of common variant polygenic risk scores, suggesting the elevated recurrence risk may be attributable to rare genetic variation. Our goal is to identify specific rare risk alleles in these families that may help to elucidate the biological significance of the common variant signals from genome-wide association studies. His lab’s work on alcohol dependence is currently focused on 1) exome sequencing in cases to investigate the impact of rare variation and 2) following up significant hits from genome-wide association studies. An area of emerging interest in our alcohol project is the role of long non-coding RNA genes and molecules in regulatory processes and risk of alcohol dependence.

Outside of work, Dr. Riley enjoys music, cooking, cycling, mountains, maps, and the road less traveled, preferably in the company of friends.

Article by Elizabeth Long.

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