Rare Genetic Variations More Frequent in Schizophrenia

To print: Select File and then Print from your browser's menu
---------------------------------------------------------------------------------------
Title: Rare Genetic Variations More Frequent in Schizophrenia
URL: http://www.pslgroup.com/dg/226A6A.htm
Doctor's Guide
July 30, 2008

BETHESDA, Md -- July 30, 2008 -- People with schizophrenia bear an increased burden of rare deletions and duplications of genetic material, genome-wide, according to a study published online in the July 30 edition of Nature.

"Although many of us have these changes in our genetic material, they are about 15% more frequent in people with schizophrenia," said Pamela Sklar, MD, Harvard University, Boston, Massachusetts, and Stanley Center for Psychiatric Research, Cambridge, Massachusetts.

"We also discovered 2 large areas of chromosomal deletions that confer a great deal of risk for schizophrenia and confirm involvement of a third previously reported area."

"By implicating 2 previously unknown sites, this study triples the number of genomic areas definitely linked to schizophrenia," said R. Thomas Insel, MD, National Institute of Mental Health, Bethesda, Maryland.

"It also confirms in a large sample that unraveling the secrets of rare structural genetic variation may hold promise for improved diagnosis, treatment, and prevention of such neurodevelopmental disorders."

Although recent smaller studies have identified such structural genetic glitches in schizophrenia, this genome-wide association study is the first large enough to detect weak signals that might otherwise be drowned out amid a din of statistical noise.

Dr. Sklar and colleagues in the International Schizophrenia Consortium team scanned the genomes of 3,391 schizophrenia cases and 3,181 controls in a European sample.

The cases showed a subtle, but statistically significant, increased number of such variations, which were found in 13.1% of cases and 10.4% of controls. Variations affected 1.41-fold more genes in people with schizophrenia, who also had a 1.45-fold higher prevalence of the rarest glitches -- those that occurred only once.

The large sample also allowed the researchers to pinpoint previously undiscovered chromosomal locations associated with schizophrenia. An area on chromosome 15 harboured deletions in 9 cases and in no controls, while an area on chromosome 1 had deletions in 10 cases and only in 1 control.

"This tells us that variations in both of these areas are very potent risk factors for schizophrenia," said Dr. Sklar.

The researchers also confirmed in 13 cases a previously reported association between schizophrenia and a deletion on chromosome 22 known to cause velocardiofacial syndrome. Other suspect sites identified were on chromosomes 12 and 16 and in genes relevant to neural development and growth.

According to the researchers, exactly how the subtly increased number of structural variations in schizophrenia might translate into illness remains to be discovered.

SOURCE: US National Institutes of Health

http://www.docguide.com

Return to News Story Page

webmaster@pslgroup.com