Corporate Banner
Satellite Banner
Genotyping & Gene Expression
Scientific Community
Become a Member | Sign in
Home>News>This Article

Genetic Analysis Reveals Insights into Genetics of OCD, Tourette’s

Published: Tuesday, November 05, 2013
Last Updated: Tuesday, November 05, 2013
Bookmark and Share
Major differences between the genetic makeup of obsessive-compulsive disorder and Tourette’s syndrome, providing the first direct confirmation that both are highly heritable.

“Both TS and OCD appear to have a genetic architecture of many different genes—perhaps hundreds in each person—acting in concert to cause disease,” said Jeremiah Scharf, assistant professor of neurology at Harvard Medical School and senior corresponding author of the report. “By directly comparing and contrasting both disorders, we found that OCD heritability appears to be concentrated in particular chromosomes, particularly chromosome 15, while TS heritability is spread across many different chromosomes.”

An anxiety disorder characterized by obsessions and compulsions that disrupt the lives of patients, OCD is the fourth-most common psychiatric illness. TS is a chronic disorder characterized by motor and vocal tics that usually begins in childhood and is often accompanied by conditions like OCD or attention-deficit hyperactivity disorder. Both conditions have been considered to be heritable, since they are known to often recur in close relatives of affected individuals, but identifying specific genes that confer risk has been challenging.

Two reports published last year in the journal Molecular Psychiatry, with leadership from Scharf and several co-authors of the current study, described genome-wide association studies (GWAS) of thousands of affected individuals and controls. While those studies identified several gene variants that appeared to increase the risk of each disorder, none of the associations were strong enough to meet the strict standards of genome-wide significance. Since the GWAS approach is designed to identify relatively common gene variants and it has been proposed that OCD and TS might be influenced by a number of rare variants, the research team adopted a different method. Called genome-wide complex trait analysis (GCTA), the approach allows simultaneous comparison of genetic variation across the entire genome, rather than the GWAS method of testing sites one at a time, as well as estimating the proportion of disease heritability caused by rare and common variants.

“Trying to find a single causative gene for diseases with a complex genetic background is like looking for the proverbial needle in a haystack,” said Lea Davis, a UChicago research assistant professor and co-corresponding author of the PLOS Genetics report. “With this approach, we aren’t looking for individual genes. By examining the properties of all genes that could contribute to TS or OCD at once, we’re actually testing the whole haystack and asking where we’re more likely to find the needles.”

Using GCTA, the researchers analyzed the same genetic datasets screened in the Molecular Psychiatry reports—almost 1,500 individuals affected with OCD compared with more than 5,500 controls, and nearly TS 1,500 patients compared with more than 5,200 controls. To minimize variations that might result from slight difference in experimental techniques, all genotyping was done by collaborators at the Broad Institute of Harvard University and MIT, who generated the data at the same time using the same equipment. Davis was able to analyze the resulting data on a chromosome-by-chromosome basis, along with the frequency of the identified variants and the function of variants associated with each condition.

The results found that the degree of heritability for both disorders captured by GWAS variants is actually quite close to what previously was predicted based on studies of families impacted by the disorders. “This is a crucial point for genetic researchers, as there has been a lot of controversy in human genetics about what is called ‘missing heritability,’” explained Scharf. “For many diseases, definitive genome-wide significant variants account for only a minute fraction of overall heritability, raising questions about the validity of the approach. Our findings demonstrate that the vast majority of genetic susceptibility to TS and OCD can be discovered using GWAS methods. In fact, the degree of heritability captured by GWAS variants is higher for TS and OCD than for any other complex trait studied to date.”

Nancy Cox, section chief of Genetic Medicine at UChicago and co-senior author of the PLOS Genetics report, added, “Despite the fact that we confirm there is shared genetic liability between these two disorders, we also show there are notable differences in the types of genetic variants that contribute to risk. TS appears to derive about 20 percent of genetic susceptibility from rare variants, while OCD appears to derive all of its susceptibility from variants that are quite common, which is something that has not been seen before.”

In terms of the potential impact of the risk-associated variants, about half the risk for both disorders appears to be accounted for by variants already known to influence the expression of genes in the brain. Further investigation of those findings could lead to identification of the affected genes and how the expression changes contribute to the development of TS and OCD. Additional studies in even larger patient populations, some of which are in the planning stages, could identify the biologic pathways disrupted in the disorder, potentially leading to new therapeutic approaches.

Further Information
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 2,600+ scientific posters on ePosters
  • More than 3,800+ 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 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

Researchers Identify ‘Fat Gene’ Associated with Obesity
Mutations within the gene FTO have been implicated as the strongest genetic determinant of obesity risk in humans, but the mechanism behind this link remained unknown.
Monday, March 17, 2014
Personalized Medicine Can Cut Breast Cancer Risk
The time has come for breast cancer risk assessment, counseling and genetic testing to move from cancer specialists to the realm of primary care, according to a presentation at the AAAS annual meeting.
Monday, February 18, 2008
Scientific News
Chromosomal Chaos
Penn study forms basis for future precision medicine approaches for Sezary syndrome
Shaking Up the Foundations of Epigenetics
Researchers at the Centre for Genomic Regulation (CRG) and the University of Barcelona (UB) published a study that challenges some of the current beliefs about epigenetics.
Cell's Waste Disposal System Regulates Body Clock Proteins
New way to identify interacting proteins could identify potential drug targets.
Compound Doubles Up On Cancer Detection
Researchers have found that tagging a pair of markers found almost exclusively on a common brain cancer yields a cancer signal that is both more obvious and more specific to cancer.
Lung Repair and Regeneration Gene Discovered
New role for hedgehog gene offers better understanding of lung disease.
Mixed Up Cell Transportation Key Piece of ALS and Dementia Puzzle
Researchers from the University of Toronto are one step closer to solving this incredibly complex puzzle, offering hope for treatment.
Five New Genetic Variants Linked to Brain Cancer Identified
The biggest ever study of DNA from people with glioma – the most common form of brain cancer – has discovered five new genetic variants associated with the disease.
Predictive Model for Breast Cancer Progression
Biomedical engineers have demonstrated a proof-of-principle technique that could give women and their oncologists more personalized information to help them choose options for treating breast cancer.
New Hope for Personalized Treatment of Eczema
Pharmaceutical researchers at Oregon State University have developed a new approach to treat eczema and other inflammatory skin disorders that would use individual tests and advanced science to create personalized treatments based on each person's lipid deficiencies.
Gene Expression: A Snapshot of Stem Cell Development
New genes found that regulate development of stem cells.
Skyscraper Banner

Skyscraper Banner
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos