Navigation Links
Largest study of its kind implicates gene abnormalities in bipolar disorder
Date:8/17/2008

The largest genetic analysis of its kind to date for bipolar disorder has implicated machinery involved in the balance of sodium and calcium in brain cells. Researchers supported in part by the National Institute of Mental Health, part of the National Institutes of Health, found an association between the disorder and variation in two genes that make components of channels that manage the flow of the elements into and out of cells, including neurons.

"A neuron's excitability whether it will fire hinges on this delicate equilibrium," explained Pamela Sklar, M.D., Ph.D., of Massachusetts General Hospital (MGH) and the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, who led the research. "Finding statistically robust associations linked to two proteins that may be involved in regulating such ion channels and that are also thought to be targets of drugs used to clinically to treat bipolar disorder is astonishing."

Although it's not yet known if or how the suspect genetic variation might affect the balance machinery, the results point to the possibility that bipolar disorder might stem, at least in part, from malfunction of ion channels.

Sklar, Shaun Purcell, Ph.D., also of MGH and the Stanley Center, and Nick Craddock, M.D., Ph.D., of Cardiff University and the Wellcome Trust Case Control Consortiuum in the United Kingdom and a large group of international collaborators report on their findings online Aug. 17, 2008 in Nature Genetics.

"Faced with little agreement among previous studies searching for the genomic hot spots in bipolar disorder, these researchers pooled their data for maximal statistical power and unearthed surprising results," said NIMH Director Thomas R. Insel, M.D. "Improved understanding of these abnormalities could lead to new hope for the millions of Americans affected by bipolar disorder."

In the first such genome-wide association study for bipolar disorder, NIMH researchers last fall reported the strongest signal associated with the illness in a gene that makes an enzyme involved the action of the anti-manic medication lithium. However, other chromosomal locations were most strongly associated with the disorder in two subsequent studies.

Since bipolar disorder is thought to involve many different gene variants, each exerting relatively small effects, researchers need large samples to detect relatively weak signals of illness association.

To boost their odds, Sklar and colleagues pooled data from the latter two previously published and one new study of their own. They also added additional samples from the STEP-BD study and Scottish and Irish families, and controls from the NIMH Genetics Repository. After examining about 1.8 million sites of genetic variation in 10,596 people including 4,387 with bipolar disorder the researchers found the two genes showing the strongest association among 14 disorder-associated chromosomal regions.

Variation in a gene called Ankyrin 3 (ANK3) showed the strongest association with bipolar disorder. The ANK3 protein is strategically located in the first part of neuronal extensions called axons and is part of the cellular machinery that decides whether a neuron will fire. Co-authors of the paper had shown last year in mouse brain that lithium, the most common medication for preventing bipolar disorder episodes, reduces expression of ANK3.

Variation in a calcium channel gene found in the brain showed the second strongest association with bipolar disorder. This CACNA1C protein similarly regulates the influx and outflow of calcium and is the site of interaction for a hypertension medication that has also been used in the treatment of bipolar disorder.


'/>"/>

Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
Source:Eurekalert

Related biology news :

1. Exploited fish make rapid comeback in worlds largest no-take marine reserve network
2. Largest ever acoustics meeting is next month from June 30 to July 4, in Paris, France
3. Findings released from 1 of the largest percutaneous coronary intervention trials ever
4. University of Minnesota to host worlds largest conference on evolution
5. Largest ever study of genetics of common disease just got bigger
6. Worlds largest marine protected area created in Pacific Ocean
7. Worlds largest investor coalition seeks further disclosure on climate change and shareholder value
8. Single-largest biodiversity survey says primary rainforest is irreplaceable
9. Largest study to investigate risk factors of autism to begin enrolling families
10. Sweets make young horses harder to train in Montana State study
11. Light receptors in eye play key role in setting biological clock, study shows
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/12/2016)... 12, 2016 WearablesResearch.com , a brand ... overview results from the Q1 wave of its quarterly ... was consumers, receptivity to a program where they would ... health insurance company. "We were surprised to ... Michael LaColla , CEO of Troubadour Research, "primarily ...
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 ... of Infosys (NYSE: INFY ), and Samsung SDS, ... partnership that will provide end customers with a more ... payment services.      (Logo: http://photos.prnewswire.com/prnh/20130122/589162 ) ... financial services, but it also plays a fundamental part in ...
(Date:4/26/2016)... April 27, 2016 Research ... Multi-modal Biometrics Market 2016-2020"  report to their offering.  ... The analysts forecast the global multimodal ... 15.49% during the period 2016-2020.  Multimodal ... sectors such as the healthcare, BFSI, transportation, automotive, ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and ... and the 6000i models are higher end machines that use the more unconventional z-dimension ... light beam from the bottom of the cuvette holder. , FireflySci has developed ...
(Date:6/23/2016)... June 23, 2016   Boston Biomedical , ... compounds designed to target cancer stemness pathways, announced ... granted Orphan Drug Designation from the U.S. Food ... gastric cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin ... to inhibit cancer stemness pathways by targeting STAT3, ...
(Date:6/23/2016)... (PRWEB) , ... June 23, 2016 , ... ... Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute approval ... of microbial tests introduced last year,” stated Bob Salter, Vice President of Regulatory ...
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the Industry Network for ... Design Lab . Located in Pasadena, Calif., the Design Lab’s mission is to ... are designed, built and brought to market. , The Design Lab is Supplyframe’s ...
Breaking Biology Technology: