PSYCHOLOGY: DISORDERS: SCHIZOPHRENIA : PSYCHOLOGY: DISORDERS: BIPOLAR DISORDER : BIOLOGY: HUMAN: GENETICS: Schizophrenia and Bipolar Disorder Share Genetic Roots

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PSYCHOLOGY: DISORDERS: SCHIZOPHRENIA : PSYCHOLOGY: DISORDERS: BIPOLAR DISORDER : BIOLOGY: HUMAN: GENETICS: Schizophrenia and Bipolar Disorder Share Genetic Roots

David P. Dillard
Administrator


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PSYCHOLOGY: DISORDERS: SCHIZOPHRENIA :
PSYCHOLOGY: DISORDERS: BIPOLAR DISORDER :
BIOLOGY: HUMAN: GENETICS:
Schizophrenia and Bipolar Disorder Share Genetic Roots



Date: Wed, 1 Jul 2009 15:51:55 -0400
From: "NIH OLIB (NIH/OD)" <[hidden email]>
To: [hidden email]
Subject:  Schizophrenia and Bipolar Disorder Share Genetic Roots



U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News



National Institute of Mental Health (NIMH)<http://www.nimh.nih.gov/>



Embargoed for Release: Wednesday, July 1, 2009, 1:00 PM EDT




CONTACT:

Jules Asher

NIMH Press Office

301-443-4536

e-mail:

[hidden email]




SCHIZOPHRENIA AND BIPOLAR DISORDER SHARE GENETIC ROOTS



Chromosomal Hotspot of Immunity/Gene Expression Regulation Implicated



A trio of genome-wide studies -- collectively the largest to date -- have
pinpointed a vast array of genetic variation that cumulatively may account
for at least one third of the genetic risk for schizophrenia. One of the
studies traced schizophrenia



<http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml>



and bipolar disorder



<http://www.nimh.nih.gov/health/topics/bipolar-disorder/index.shtml>


in part, to the same chromosomal neighborhoods.


"These new results recommend a fresh look at our diagnostic categories,"
said Thomas R. Insel, M.D., director of the National Institute of Mental
Health (NIMH), part of the National Institutes of Health.  "If some of the
same genetic risks underlie schizophrenia and bipolar disorder, perhaps
these disorders originate from some common vulnerability in brain
development."

Three schizophrenia genetics research consortia, each funded in part by
NIMH, report separately on their genome-wide association studies



<http://www.genome.gov/20019523>



online July 1, 2009, in the journal Nature. However, the SGENE,
International Schizophrenia (ISC) and Molecular Genetics of Schizophrenia
(MGS) consortia shared their results - making possible meta-analyses of a
combined sample totaling 8,014 cases and 19,090 controls.

All three studies implicate an area of Chromosome 6 (6p22.1), which is
known to harbor genes involved in immunity and controlling how and when
genes turn on and off. This hotspot of association might help to explain
how environmental factors affect risk for schizophrenia. For example,
there are hints of autoimmune



<http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html>



involvement in schizophrenia, such as evidence that offspring of mothers
with influenza while pregnant have a higher risk of developing the
illness.

"Our study was unique in employing a new way of detecting the molecular
signatures of genetic variations with very small effects on potential
schizophrenia risk," explained Pamela Sklar, M.D., Ph.D., of Harvard
University and the Stanley Center for Psychiatric Research, who co-led the
ISC team with Harvard's Shaun Purcell, Ph.D.

"Individually, these common variants' effects do not all rise to
statistical significance, but cumulatively they play a major role,
accounting for at least one third -- and probably much more -- of disease
risk," said Purcell.

Among sites showing the strongest associations with schizophrenia was a
suspect area on Chromosome 22 and more than 450 variations in the suspect
area on Chromosome 6. Statistical simulations confirmed that the findings
could not have been accounted for by a handful of common gene variants
with large effect or just rare variants. This involvement of many common
gene variants suggests that schizophrenia in different people might
ultimately be traceable to distinct disease processes, say the
researchers.

"There was substantial overlap in the genetic risk for schizophrenia and
bipolar disorder that was specific to mental disorders," added Sklar. "We
saw no association between the suspect gene variants and half a dozen
common non-psychiatric disorders."

Still, most of the genetic contribution to schizophrenia, which is
estimated to be at least 70 percent heritable, remains unknown.

"Until this discovery, we could explain just a few percent of this
contribution; now we have more than 30 percent accounted for," said Thomas
Lehner, Ph.D., MPH, chief of NIMH's Genomics Research Branch



<http://www.nimh.nih.gov/about/organization/
dnbbs/genomics-research-branch/index.shtml>



"The new findings tell us that many of these secrets have been hidden in
complex neural networks, providing hints about where to look for the still
elusive -- and substantial -- remaining genetic contribution."

The MGS consortium pinpointed an association between schizophrenia and
genes in the Chromosome 6 region that code for cellular components that
control when genes turn on and off. For example, one of the strongest
associations was seen in the vicinity of genes for proteins called
histones



<http://nihroadmap.nih.gov/epigenomics/epigeneticmechanisms.asp>



that slap a molecular clamp on a gene's turning on in response to the
environment. Genetically rooted variation in the functioning of such
regulatory mechanisms could help to explain the environmental component
repeatedly implicated in schizophrenia risk.

The MGS study also found an association between schizophrenia and a
genetic variation on Chromosome 1 (1p22.1) which has been implicated in
multiple sclerosis, an autoimmune disorder.

"Our study results spotlight the importance not only of genes, but also
the little-known DNA sequences between genes that control their
expression," said Pablo Gejman, M.D., of the NorthShore University
HealthSystem Research Institute, of Evanston, ILL, who led the MGS
consortium team. "Advances in biotechnology, statistics, population
genetics, and psychiatry, in combination with the ability to recruit large
samples, made the new findings possible."

The SGENE consortium study pinpointed a site of variation in the suspect
Chromosome 6 region that could implicate processes related to immunity and
infection. It also found significant evidence of association with
variation on Chromosomes 11 and 18 that could help account for the
thinking and memory deficits of schizophrenia.

The new findings could eventually lead to multi-gene signatures or
biomarkers for severe mental disorders. As more is learned about the
implicated gene pathways, it may be possible to sort out what's shared by,
or unique to, schizophrenia and bipolar disorder, the researchers say.



<www.nimh.nih.gov/images1/news-items/sklarschizbp-overlapgraph.jpg>




Schizophrenia and bipolar disorder share genetic roots that appear to be
specific to serious mental disorders, and are not shared by
non-psychiatric illnesses. Bars representing different study samples show
that the same genetic variations that account for risk in both mental
disorders account for virtually none of the risk for coronary artery
disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid
arthritis (RA), or Type 1 (T1D) or Type 2 (T2D) diabetes. Source:
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic
Research, Harvard University.



The mission of the NIMH is to transform the understanding and treatment of
mental illnesses through basic and clinical research, paving the way for
prevention, recovery and cure. For more information, visit the



<http://www.nimh.nih.gov>




The National Institutes of Health (NIH) -- The Nation's Medical Research
Agency -- includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. It is the primary federal
agency for conducting and supporting basic, clinical and translational
medical research, and it investigates the causes, treatments, and cures
for both common and rare diseases. For more information about NIH and its
programs, visit



<http://www.nih.gov>





----------------



REFERENCES:



Jianxin S, et al.
Common variants on chromosome 6p22.1 are associated with schizophrenia.
July 1, 2009, "Nature"



Stefansson H, et al.
Common variants conferring risk of schizophrenia.
July 1, 2009, "Nature"



Purcell SM, et al.
Common polygenic variation contributes to risk of
schizophrenia that overlaps with bipolar disorder.
July 1, 2009, "Nature"




##




This NIH News Release is available online at:
<http://www.nih.gov/news/health/jul2009/nimh-01.htm>




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