Navigation Links
Family studies suggest rare genetic mutations team up to cause schizophrenia
Date:5/28/2013

Using a novel method of analyzing genetic variations in families, researchers at Johns Hopkins have found that individually harmless genetic variations affecting related biochemical processes may team up to increase the risk of schizophrenia. They say their findings, reported May 28 in Translational Psychiatry, bring some clarity to the murky relationship between genetics and schizophrenia, and may lead to a genetic test that can predict which medications will be effective for individual patients.

"It's long been clear that schizophrenia runs in families, but schizophrenia as a simple inherited disease didn't make sense from an evolutionary point of view because people with the disease tend to have fewer children and the disease-causing genetic variants shouldn't survive," says Dimitri Avramopoulos, M.D., Ph.D., an associate professor of psychiatry in the McKusick-Nathans Institute of Genetic Medicine. Moreover, he says, studies searching for schizophrenia-linked gene variants have found only weak connections to a few genes nothing that would explain the persistent prevalence of the disease, which affects about 1 percent of the population.

Most geneticists believe that the culprit in so-called complex genetic diseases such as schizophrenia is not just one genetic variant, but more than one acting in concert. It's also likely that individual cases of the disease are caused by different combinations of variants, Avramopoulos says. He and fellow researchers took this hypothesis a step further, theorizing that while our bodies can usually compensate for one faulty gene that affects a particular system, more than one hit to the same system is likely to tip people toward disease.

The research team devised a technique for analyzing gene-sequencing data that explores whether variants cluster in a subset of cases in a non-random way. After finding support for their hypothesis in previously obtained data on 123 families with at least two schizophrenia-affected members, they decided to sequence genes connected through a biochemical chain reaction that has been linked to the disease in 48 inpatients. Known as the neuregulin signaling pathway, that chain reaction relays signals within the nervous system.

As they had predicted, the researchers found that some of the families had multiple neuregulin signaling-related variants while others had none, a distribution that was highly unlikely to result from chance. Moreover, the schizophrenia patients with neuregulin signaling variants experienced more hallucinations but less impairment than the other schizophrenia patients in the study.

"These results support the idea that there's no single genetic recipe for schizophrenia, but that a buildup of mutations in a pathway related to the disease like neuregulin signaling can be the culprit," Avramopoulos says. "The results are also evidence for the current theory that schizophrenia isn't a single disease at all, but a suite of related disorders." Those patients in the study who did not have neuregulin signaling-related variants likely carried variants in a different pathway instead, he notes.

While the results of the study were surprisingly clear-cut given the small number of families in the study, Avramopoulos cautions that larger studies are needed to confirm the results before drawing any firm conclusions. He also plans to study the exact roles of the schizophrenia-linked variants the team identified. Finally, the encouraging results mean it would be worthwhile to apply the new analytic method to other common diseases, such as diabetes and heart disease, which also appear to have complex genetic roots.


'/>"/>

Contact: Shawna Williams
shawna@jhmi.edu
410-955-8236
Johns Hopkins Medicine
Source:Eurekalert

Related biology news :

1. Merkin Family Foundation to fund next generation of Broad Institute scientists
2. Family history of liver cancer increases risk of developing the disease
3. Starting a family does not encourage parents to eat healthier
4. Discovery of a new family of key mitochondrial proteins for the function and viability of the brain
5. Family values
6. FirstMark Exhibiting and Presenting at the San Diego Academy of Family Physicians 55th Annual Postgraduate Symposium
7. Parkinsons disease gene identified with help of Mennonite family: UBC-VCH research
8. Helping family is key for social birds
9. Millipede family added to Australian fauna
10. CEVA, Rubidium Partner to Deliver Speech Processing Solutions based on the CEVA-TeakLite Family of DSPs
11. Bloomberg School receives $28 million for family planning advocacy
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/11/2016)... --> --> ... Recognition Market by Technology (Pattern Recognition), by Component (Hardware, ... Type (On-Premises and Cloud), by Industry Vertical and by ... the global market is expected to grow from USD ... 2020, at a CAGR of 19.1%. , ...
(Date:3/9/2016)... March 9, 2016  Crossmatch ® , a ... solutions, today announced the addition of smart features ... multi-factor authentication platform. New contextual and application-specific ... step-up security where it,s needed most — while ... DC . --> Washington, ...
(Date:3/2/2016)... , March 2, 2016 ... the addition of the  "Global Biometrics Market ... offering.  ,     (Logo: http://photos.prnewswire.com/prnh/20130307/600769) , , Global ... grow at a CAGR of around 27% ... ) has announced the addition of the  ...
Breaking Biology News(10 mins):
(Date:4/26/2016)... ... April 27, 2016 , ... Cameron Cushman ... an associate in the firm’s Intellectual Property practice group. , Clients turn to ... applications. He has an electrical engineering and computer engineering background, and experience in ...
(Date:4/26/2016)... ... ... Mr. Palmer created the RPO business for Ceridian and lead the Public ... contract in the U.S. intelligence community with The SI (a Lockheed Martin divestiture). , ... of Accolo. “We are growing and his experience guiding our expansion is unparalleled. ...
(Date:4/26/2016)... and MIAMI , ... prize recognizes the innovation capabilities of Norma,s R&D ... benefit patients and laboratory diagnostics globally. ... Norma Instruments , an innovative technology ... the field of hematology, announced today that it ...
(Date:4/26/2016)... , April 26, 2016 Celsion ... development company, today announced that the first patient ... enrolled in its ongoing global Phase III OPTIMA ... of doxorubicin, in combination with radiofrequency ablation standardized ... treat newly diagnosed patients with primary liver cancer, ...
Breaking Biology Technology: