NARSAD Grantee Co-Leads Mammoth Effort to Dissect Mental Illness Risk Gene

NARSAD Grantee Co-Leads Mammoth Effort to Dissect Mental Illness Risk Gene

Posted: June 24, 2013

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Many genes have come to the attention of mental illness researchers because tiny variations in them appear to increase the risk of mental illness. But one gene, dubbed DISC1, receives the lion's share of attention among mental illness researchers. DISC1 plays a role in neurodevelopment, neuronal migration and signaling, processes that are thought to be disrupted in mental illnesses. Originally dubbed, "disrupted in schizophrenia 1," because most of the handful of cases were schizophrenia, it's now clear that a break in DISC1 can also lead to other serious mental illnesses like bipolar disorder or depression.

In a new genetic study co-led by the researcher who discovered the DISC1 gene, NARSAD Grantee David J. Porteous, Ph.D. of the University of Edinburgh, U.K., started the mammoth task of combing through the very long chain of molecules—more than 500,000—that make up DISC1. The study, which was published June 4, 2013 in Molecular Psychiatry, provides the most complete look at the DISC1 gene to date.

Although several small genetic studies have implicated single nucleotide polymorphisms (SNPs) in DISC1 with risk for schizophrenia, bipolar disorder, or major depression, these results have not been supported in meta-analyses or large-scale genome wide association studies. The researchers from University of Edinburgh and Cold Spring Harbor Laboratory, NY, examined the DNA sequence of DISC1 in over 1,500 subjects, and catalogued nearly 3,000 minute differences in links of the molecular chain.

The current study identified 12 of the 17 rare coding SNPs that have previously been reported for DISC1. In addition, the researchers identified eight more non-synonymous SNPs for a total of 20 DISC1 SNPs that lead to changes in the amino acid sequence of the protein. Using applied prediction algorithms, the researchers identified five that are likely to be deleterious.

Overall, the current study suggests that there is a high level of sequence variation in DISC1 that has yet to be discovered―helping guide future studies and possibly the development of future treatments and/or predictive measures.

Read more about the study on the Brain & Behavior Research Foundation-sponsored website Schizophrenia Research Forum

Read the Study Abstract on PubMed