Landmark Study Shows Common Genetic Links Across 5 Major Psychiatric Disorders

Jordan W. Smoller, M.D., Sc.D. expert in mental health research
Jordan W. Smoller, M.D., Sc.D.

From The Quarterly, Spring 2013

The Cross-Disorder Group of the Psychiatric Genomics Consortium (PGC), a consortium of geneticists and neuroscientists, has released the results of a worldwide, six-year-long collaboration in the first genome-wide search for single-“letter” genetic variations (called SNPs, or single-nucleotide polymorphisms) across five psychiatric disorders. Led by Jordan W. Smoller, M.D., Sc.D. and Kenneth Kendler, M.D., as well as Nicholas Craddock, M.D., the group found genetic overlap with disorders previously thought of as distinct, including attention-deficit hyperactivity disorder (ADHD), autism, bipolar disorder, major depressive disorder (MDD), and schizophrenia.

The consortium took a novel approach by analyzing the five key disorders as if they were the same illness. The study involved researchers in 19 nations who amassed a sample consisting of 33,332 people with psychiatric illnesses and 27,888 controls.

“The major accomplishment of this collaborative effort is to begin to apply well-powered modern molecular gene-tic techniques to attempting to answer one of the oldest questions in psychiatry: ‘What are the etiological relationships between our major psychiatric disorders?’” says Dr. Kendler.

The findings of the study were published in The Lancet and point to at least four locations in the human genome that appear to confer a risk that cuts across the five disorders. Two of them occur in genes that encode proteins that are important in a class of tiny pores called calcium channels that regulate the flow of calcium into cells.

“The finding that calcium channel signaling genes are involved in multiple psychiatric disorders raises the possibility that targeting this pathway might offer new opportunities for treatment,” says Dr. Smoller. He also hopes that studies like this one will lead to improved diagnostic tools for the disorders. While each of the individual genetic associations identified account for a small amount of risk for mental illness, the study opens the door for further investigation of the overlapping areas identified. With continuing research that identifies causes of illness, diagnostics for mental illness based on neuroscience and genetics, in addition to observed behavior, become an achievable goal.

Also involved in the study were: Scientific Council Members: Huda Akil, Ph.D.; Jack D. Barchas, M.D.; Wade H. Berrettini, M.D., Ph.D.; Joseph D. Buxbaum, Ph.D.; William F. Byerley, M.D.; Robert R. Freedman, M.D.; Elliott S. Gershon, M.D.; John R. Kelsoe, M.D.; James L. Kennedy, M.D., Ph.D.; Jeffrey A. Lieberman, M.D.; Anil K. Malhotra, M.D.; James B. Potash, M.D., M.P.H.; Alan F. Schatzberg, M.D.; and NARSAD Grantees: Ayman Fanous, M.D.; Thomas B. Barrett, M.D.; Michael Bauer, M.D., Ph.D.; Frank Bellivier, M.D., Ph.D.; Sarah E. Bergen, M.S., Ph.D., Joseph Biederman, M.D., Elisabeth B. Binder, Ph.D., Dorret I. Boomsma, M.A., Ph.D.; Gerome Breen, Ph.D.; Margit Burmeister, Ph.D.; David A. Collier, Ph.D.; Jubao Duan, Ph.D.; Nelson B. Freimer, M.D.; Pablo V. Gejman, M.D.; Elaine K. Green, Ph.D.; Tiffany A. Greenwood, Ph.D.; Hugh Gurling, M.D.; Steven P. Hamilton, M.D., Ph.D.; Witte J. Hoogendijk, M.D., Ph.D.; Stéphane Jamain, Ph.D.; Edward G. Jones, M.D., Ph.D.; James A. Knowles, M.D., Ph.D.; Todd Lencz, Ph.D.; Jun Li, Ph.D.; Chunyu Liu, Ph.D.; Falk W. Lohoff, M.D.; Patrick J. McGrath, M.D.; Melvin G. McInnis, M.D.; Andrew McIntosh, M.D.; Francis J. McMahon, M.D.; Pierandrea Muglia, M.D.; Stan F. Nelson, M.D.; Ann Olincy, M.D.;  Roel A. Ophoff, Ph.D.; Urban Osby, M.D., Ph.D.; Carlos N. Pato, M.D.; Michele T. Pato, M.D.; Roy H. Perlis, M.D., M.Sc.; Shaun M. Purcell, Ph.D.; Brien Riley, M.Sc., Ph.D.; Guy Rouleau, M.D., Ph.D.; Dan Rujescu, M.D.; Alan R. Sanders, M.D.; Martin Schalling, M.D., Ph.D.; Thomas G. Schulze, M.D.; Paul D. Shilling, Ph.D.; Pamela Sklar, M.D., Ph.D.; T. Scott Stroup, M.D., M.P.H.; Robert C. Thompson, Ph.D.; Edwin J.C.G. van den Oord, Ph.D.;  John B. Vincent, Ph.D.; Stanley J. Watson, M.D., Ph.D.; Myrna M. Weissman, Ph.D.; Allan H. Young, M.D., Ph.D.; Peter P. Zandi, Ph.D.