Large International Study Supports Common Genetic Contributions to Mental Illness

Article Content

A large international research consortium has identified several new genes associated with both bipolar disorder and schizophrenia.  Their study, co-authored by psychiatric researchers from the University of California, San Diego School of Medicine, reveals that common genetic variants contribute to a person’s risk of schizophrenia and bipolar disorder.

The findings, reported by the Psychiatric Genome-Wide Association Study Consortium (PGC) and published online today in two papers in the journal Nature Genetics, provide new molecular evidence that 11 genetic regions have strong, robust, and replication association with these diseases, including six regions not previously observed. The researchers also found that many DNA variations contribute to both diseases.

“These findings represent a major advance that will help us understand the cause of bipolar disorder and schizophrenia, and in the development of new treatments for these chronic, severe and debilitating disorders,” said John Kelsoe, MD, professor of psychiatry at UC San Diego and co-chair of the Psychiatric GWAS Consortium for Bipolar Disorder, whose lab played a major role in this work.

Schizophrenia and bipolar disorder are common and often devastating brain disorders. Some of the most prominent symptoms in schizophrenia are persistent delusions, hallucinations and cognitive problems. Bipolar disorder (or manic-depressive illness) is characterized by episodes of severe mood problems including mania and depression. Both affect about 1 percent of the world’s population and usually strike in late adolescence or early adulthood. Despite the availability of treatments, these illnesses are usually chronic, and response to treatment is often incomplete leading to prolonged disability and personal suffering. Family history, which reflects genetic inheritance, is a strong risk factor for both schizophrenia and bipolar disorder, and it has generally been assumed that dozens of genes, along with environmental factors, contribute to disease risk.

Kelsoe said that the studies employed a powerful genomics mapping technology called genome-wide association, an approach that involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease. “In our paper on bipolar disorder, a million DNA markers were examined in more than 12,000 patients with bipolar disorder and 49,000 control subjects,” said Kelsoe, who is a member of the Department of Psychiatry and the Institute for Genomic Medicine at UC San Diego.

Formed in 2007, the PGC is the largest consortium ever in psychiatry in which more than 250 researchers in 20 countries have come together to advance knowledge of the genetic causes of mental illness. These groups have shared genetic data from tens of thousands of patients collected over many years.

The research was funded by the U.S. National Institute of Mental Health, as well as numerous European, U.S., and Australian funding bodies.