While the genetics of schizophrenia is a murky area, this is an interesting
and suggestive result. Our understanding of the importance of copy number
variants, of course, is one of the major contributions of the human genome



*Volume 87
Number 2
August 2010*

***The embargo has lifted on this article.***
Large risk schizophrenia marker revealed

*Download Article<>

A group of scientists has identified a genetic variant that substantially
increases the risk for developing schizophrenia in Ashkenazi Jewish and
other populations. The study, published by Cell Press on August 5th in the
American Journal of Human Genetics, associates a deletion on chromosome 3
with increased incidence of schizophrenia.

Schizophrenia is a psychiatric illness that affects ~1% of the world
population. Characterized by delusions, hallucinations, and disorganized
thinking, it is a devastating disorder.

A group of researchers led by Stephen Warren, Ph.D., from Emory University
studied the genetics of schizophrenia by analyzing the prevalence of copy
number variants (CNVs) in schizophrenic patients. CNVs are changes in the
number of copies of DNA segments throughout the human genome. The
researchers began by looking at Ashkenazi Jewish subjects already under
study by collaborating scientist Ann E. Pulver, Sc.D. and her team at Johns
Hopkins University. The Emory group found an excess of large, rare CNVs in
these schizophrenic cases compared to controls.

Combining their analysis with those of previous CNV studies of schizophrenic
patients, Warren and his colleagues identify a CNV, specifically, a deletion
at 3q29, that associates with schizophrenia with an odds ratio (a measure of
effect size) of 16.98. “This odds ratio rivals that of any genome-wide
association study of schizophrenia and suggests that the 3q29 deletion
confers a significant risk for this severe psychiatric phenotype,” explains
Warren. An odds ratio of 17 means someone with this deletion is 17 times
more likely to develop schizophrenia than someone without the deletion.

This research also highlights candidate genes contained within the deletion
that may also be associated with schizophrenia. “Two genes, PAK2 and DLG1,
are of particular note as paralogs of these genes are known to be associated
with intellectual disability” states Jennifer Mulle, Ph.D., a member of the
Emory team. Research is finding that the same or similar variants are
associated with related complex disorders and traits. “These exciting
results imply the interval at chromosome 3q29 may harbor additional genetic
mutations that contribute to schizophrenia susceptibility,” continues Dr.

If this study is any indication of what lies ahead, a great deal of the
missing heritability of complex disorders may be revealed by studying CNVs.
“Such rare deletions may be the single most fruitful approach to begin to
unravel the mechanism of schizophrenia (and other disorders) as they
illuminate genes that provide the substrate for further study,” concludes


The researchers include: *See PDF*

Warren, Mulle et al.: “Microdeletions of 3q29 Confer High Risk for
Schizophrenia.” Publishing in the *American Journal of Human Genetics*,
September 10, 2010. doi:10.1016/j.ajhg.2010.07.013

*Author Contact: *Mulle, at Emory University School of Medicine, Atlanta,
GA, at [log in to unmask]; and Warren, at Emory University School of Medicine,
Atlanta, GA, at [log in to unmask]

Michael Balter
Contributing Correspondent, Science
Adjunct Professor of Journalism,
New York University

Email:  [log in to unmask]

"When I give food to the poor, they call me a saint. When I ask why the poor
have no food, they call me a Communist." -- Hélder Pessoa Câmara