Genetic Basis of Schizophrenia More Complex than Previously Thought

A significant portion of the genetic basis of schizophrenia can be traced to the cumulative effect of a large number of common genetic variants, researchers have discovered, a finding that will increase psychiatrists’ understanding of this complex disease.

The International Schizophrenia Consortium reported last year that rare chromosomal structural variants increase an individual’s risk for developing schizophrenia. Now, scientists at 11 research institutes across the world have shown that the action of thousands of common genetic variants, when examined together, are responsible for a significant increase in risk for both schizophrenia and bipolar disorder.

Patrick Sullivan, MD, Ray M. Hayworth and Family Distinguished Professor of Psychiatry in the department of genetics at the University of North Carolina School of Medicine and co-author of the study, explained that the researchers used “genechip technology” to identify 30,000 single nucleotide polymorphisms that were more common in the 3,000 study participants with schizophrenia than the 3,000 without the disease. The researchers saw this pattern in three different samples of patients with schizophrenia and two separate samples of patients with bipolar disorder, which provided the additional finding of a previously unknown overlap between the disorders to the researchers. Such “risk variants” were not seen in patients with non-psychiatric disorders like hypertension or diabetes.

According to the researchers, this finding shows that schizophrenia is “much more complex” than psychiatrists had previously thought, and, coupled with previous research, provides evidence that both rare genetic variants and common ones increase an individual’s risk for developing schizophrenia.

An additional finding of the study showed that the human leukocyte antigen (HLA) locus could be an additional risk factor for schizophrenia. The researchers are now investigating the interaction between genes and the environment and the impact of that interaction on an individual’s risk for psychiatric diseases.

“This is an enormous first for our field,” said Sullivan. “You could say that we now have the outline of the puzzle, and we just need to take all of these pieces that we have identified and see how they fit them together.”

The study’s senior author is Pamela Sklar, MD, PhD, associate director of the Department of Psychiatry and Center for Human Genetic Research at Massachusetts General Hospital, and a senior associate member of the Broad Institute of MIT and Harvard. The consortium included researchers from the University of Aberdeen, Cardiff University, University of Edinburgh, Karolinska Institutet, Massachusetts General Hospital, the Queensland Institute of Medical Research, University of Southern California, Stanley Center for Psychiatric Research at the Broad Institute of Harvard and MIT, Trinity College Dublin, and University College London

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