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HMS and Broad Institute Researchers Discover First Strong Genetic Link to Bipolar Disorder

Harvard Medical School's Gordon Hall sits across the HMS quadrangle.
Harvard Medical School's Gordon Hall sits across the HMS quadrangle. By Justin C. Wong
By Jonathan A. Cosgrove and Andrew M. Lu, Contributing Writers

A research team including scientists at Harvard Medical School and the Broad Institute of MIT and Harvard reported the first strong genetic risk factor for bipolar disorder in a study published in the journal Nature Genetics on April 1.

Researchers at HMS and the Broad Institute’s Stanley Center for Psychiatric Research analyzed the genomes of nearly 50,000 participants to identify the AKAP11 gene, which they found increases the odds of bipolar disorder by seven times. Bipolar disorder is “a severe, heritable mood disorder that affects approximately one percent of the population and often begins in early adulthood,” according to a press release from the Broad Institute.

Steven E. Hyman, director of the Stanley Center, said the study utilized innovative genetic research to analyze the origins and risk factors of bipolar disorder.

“We can use genes as a tool to stratify people to see who is at risk, and that might help us study environmental risk factors better,” Hyman said.

Benjamin Neale, co-director of the Program in Medical and Population Genetics at the Broad Institute, said he believes the study will provide important insight into the disorder.

“The long-term hope is that the genetic discoveries can form the basis of better understanding of the underlying biological processes that are involved in bipolar disorder,” Neale said.

The study explains how the AKAP11 gene influences bipolar disorder on a molecular level and how it may alter the effectiveness of certain treatments for the disorder.

Lithium, a common medication prescribed for the disorder, is not always effective and produces side effects for 75 percent of patients. The AKAP11 gene may interact with the lithium treatment, per the study.

Scientists are still working towards fully understanding the reasons behind the development of bipolar disorder and how lithium treatment can mitigate its symptoms.

The researchers plan to conduct further large-scale studies to find genetic risks for bipolar disorder across the entire human genome through sequencing analysis. They also intend to create cellular models with variants of the AKAP11 gene to better understand the mechanisms behind bipolar disorder, which would allow for better diagnoses and novel therapies.

Hyman said he believes the study of genetics is critical to understanding underlying cellular pathways.

“We do genetics above all because genes are clues to molecular mechanisms which can be clues to both better diagnoses and therapies,” he said. “And if you don’t understand what is going on in people then you’re just guessing, and guessing hasn’t gotten us very far in terms of treatments.”

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