Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Schizophrenia’s Genetic Skyline Rising

Published: Thursday, July 24, 2014
Last Updated: Thursday, July 24, 2014
Bookmark and Share
Suspect common variants soar from 30 to 108 - NIH-funded study.

The largest genomic dragnet of any psychiatric disorder to date has unmasked 108 chromosomal sites harboring inherited variations in the genetic code linked to schizophrenia, 83 of which had not been previously reported.

By contrast, the “skyline” of such suspect variants associated with the disorder contained only 5 significant peaks in 2011. By combining data from all available schizophrenia genetic samples, researchers supported by the National Institutes of Health powered the search for clues to the molecular basis of the disorder to a new level.

“While the suspect variation identified so far only explains only about 3.5 percent of the risk for schizophrenia, these results warrant exploring whether using such data to calculate an individual’s risk for developing the disorder might someday be useful in screening for preventive interventions,” explained Thomas R. Insel, M.D., director of the NIH’s National Institute of Mental Health, one funder of the study. “Even based on these early predictors, people who score in the top 10 percent of risk may be up to 20-fold more prone to developing schizophrenia.”

The newfound genomic signals are not simply random sites of variation, say the researchers. They converge around pathways underlying the workings of processes involved in the disorder, such as communication between brain cells, learning and memory, cellular ion channels, immune function and a key medication target.

The Schizophrenia Working Group of the Psychiatric Genomic Consortium (PGC) External Web Site Policy reports on its genome-wide analysis of nearly 37,000 cases and more than 113,000 controls in the journal Nature, July 21, 2014. The NIMH-supported PGC represents more than 500 investigators at more than 80 research institutions in 25 countries.

Prior to the new study, schizophrenia genome-wide studies had identified only about 30 common gene variants associated with the disorder. Sample sizes in these studies were individually too small to detect many of the subtle effects on risk exerted by such widely shared versions of genes. The PGC investigators sought to maximize statistical power by re-analyzing not just published results, but all available raw data, published and unpublished. Their findings of 108 illness-associated genomic locations were winnowed from an initial pool of about 9.5 million variants.

A comparison of the combined study data with findings in an independent sample of cases and controls suggest that considerably more such associations of this type are likely to be uncovered with larger sample sizes, say the researchers.

There was an association confirmed with variation in the gene that codes for a receptor for the brain chemical messenger dopamine, which is known to be the target for antipsychotic medications used to treat schizophrenia. Yet evidence from the study supports the view that most variants associated with schizophrenia appear to exert their effects via the turning on and off of genes rather than through coding for proteins.

The study found a notable overlap between protein-related functions of some linked common variants and rare variants associated with schizophrenia in other studies. These included genes involved in communication between neurons via the chemical messenger glutamate, learning and memory, and the machinery controlling the influx of calcium into cells.

“The overlap strongly suggests that common and rare variant studies are complementary rather than antagonistic, and that mechanistic studies driven by rare genetic variation will be informative for schizophrenia,” say the researchers.

Among the strongest associations detected, as in previous genome-wide genetic studies, was for variation in tissues involved in immune system function. Although the significance of this connection for the illness process remains a mystery, epidemiologic evidence has long hinted at possible immune system involvement in schizophrenia.

Findings confirm that it’s possible to develop risk profile scores based on schizophrenia-associated variants that may be useful in research - but for now aren’t ready to be used clinically as a predictive test, say the researchers.

They also note that the associated variations detected in the study may not themselves be the source of risk for schizophrenia. Rather, they may be signals indicating the presence of disease-causing variation nearby in a chromosomal region.

Researchers are following up with studies designed to pinpoint the specific sequences and genes that confer risk. The PGC is also typing genes in hundreds of thousands of people worldwide to enlarge the sample size, in hopes of detecting more genetic variation associated with mental disorders. Successful integration of data from several GWAS studies suggests that this approach would likely be transferrable to similar studies of other disorders, say the researchers.

“These results underscore that genetic programming affects the brain in tiny, incremental ways that can increase the risk for developing schizophrenia,” said Thomas Lehner, Ph.D., chief of NIMH’s Genomics Research Branch. “They also validate the strategy of examining both common and rare variation to understand this complex disorder.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 4,000+ scientific posters on ePosters
  • More than 5,300+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Exploring the Genome of the River Blindness Parasite
Researchers have decoded the genome of the parasite that causes the skin and eye infection known as river blindness.
Wednesday, December 07, 2016
Gene-Editing Improves Vision in Blind Rats
Scientists developed a targeted gene-replacement technique that can modify genes in both dividing and non-dividing cells in living animals.
Wednesday, December 07, 2016
Protein-Folding Gene Helps Heal Wounds
Researchers identified a protein that dramatically accelerates wound healing in animal models.
Wednesday, November 23, 2016
NIH Researchers Unveil New Wound-Healing Role for Protein-Folding Gene in Mice
The study found that topical treatment of an Hsp60-containing gel dramatically accelerates wound closure in a diabetic mouse model.
Friday, October 28, 2016
Gene Editing Corrects Sickle Cell Mutation
Researchers demonstrate a potential pathway to developing gene-editing treatments for sickle cell disease.
Wednesday, October 26, 2016
NIH Scientists Uncover Genetic Explanation for Frustrating Syndrome
Researchers at NIH have suggested that the multiple alpha tryptase gene copies might underlie health issues that affect a substantial number of people.
Tuesday, October 18, 2016
NIH Commits $6.7 M to Advance DNA, RNA Sequencing Technology
"Can you believe they make DNA sequencers the size of staplers?" asked Meni Wanunu, Ph.D. "Ideas that were crazy twenty years ago are now happening!"
Friday, October 07, 2016
“Sixth Sense” More Than a Feeling
NIH study of rare genetic disorder reveals importance of touch and body awareness.
Monday, September 26, 2016
The Genetics of Blood Pressure
Researchers have identifed areas of the genome associated with blood-pressure including 17 previously unknown loci.
Wednesday, September 21, 2016
Catalogue of Human Genetic Diversity Expands
The largest data set of human exomes to date has been assembled to better study seqence variants and their consequences.
Wednesday, September 07, 2016
$12.4M Awarded to Neural Regeneration Projects
The National Institutes of Health will fund six projects to identify biological factors that influence neural regeneration.
Friday, September 02, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
Public Support for National Study
Survey shows the majority of respondents support or show willingness for national precision medicine study.
Thursday, August 18, 2016
Schizophrenia, Autism Share Genetic Causes
Monkey brain developmental atlas pinpoints when, where genes activate.
Tuesday, August 16, 2016
How Breast Cancers Resist Chemotherapy
Researchers discovered an unexpected way that breast cancers cells with mutant BRCA1 or BRCA2 genes acquire drug resistance and evade chemotherapies.
Wednesday, August 10, 2016
Scientific News
Big Genetics in BC: The American Society for Human Genetics 2016 Meeting
Themes at this year's meeting ranged from the verification, validation, and sharing of data, to the translation of laboratory findings into actionable clinical results.
Cancer Genetics: Key to Diagnosis, Therapy
When applied judiciously, cancer genetics directs caregivers to the right drug at the right time, while sparing patients of unnecessary or harmful treatments.
Diabetes Missing Link Discovered
Researchers from the University of Auckland have shown that beta catenin plays a vital role in the control of insulin release from the pancreas.
Study Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity
Hippo pathway signaling regulates organ size by moderating cell growth, apoptosis and stem cell renewal, but dysregulation contributes to cancer development.
Gene Editing Yields Tomatoes That Ripen Weeks Earlier
Research team develop method to make tomato plants flower and ripen fruit two weeks faster than current growth rates.
Exploring the Genome of the River Blindness Parasite
Researchers have decoded the genome of the parasite that causes the skin and eye infection known as river blindness.
Gene-Editing Improves Vision in Blind Rats
Scientists developed a targeted gene-replacement technique that can modify genes in both dividing and non-dividing cells in living animals.
Unexpected Role for Epigenetic Enzymes in Cancer
Researchers use epigenetics to identify the role of an enzyme family as regulators of genetic message interpretation in yeast.
Genetic Links to Brain Cancer Cell Growth
Researchers discover clues to tumour behaviour from genetic differences between brain cancer cells and normal tissue cells.
Gene Therapy Maintains Clotting Factor for Hemophilia Patients
Following a single gene therapy dose, the highest levels of an essential blood clotting factor IX were observed in hemophilia B patients.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
4,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!