Summary: Researchers have identified a significant overlap between suicide and major depressive disorder.
Yale researchers have discovered several genetic variants that signal the risk of serious suicide attempts and noted some variants have also been linked to major depressive disorder, they report Jan. 17 in the journal Translational Psychiatry.
The whole genome analysis for the first time identified a genetic overlap between suicide attempts and major depression, the authors say.
Research has shown that suicide seems to run in families but there have been few efforts to search for genes that might confer increased risk. Worldwide, more than 800,000 people died by suicide in 2015.
Senior author Joel Gelernter, the Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, and lead author Daniel Levey, a postdoctoral researcher at Yale, wanted to find genetic variants that influence the risk of serious suicide attempts. They conducted a genome-wide association study of almost 2,500 European Americans and more than 3,800 African Americans. They ruled out those who had only ideas of suicide and instead ranked subjects by the severity of their suicide attempts — such as those requiring medical attention.
They found one variant of a gene involved in energy production that was linked to suicide severity in European Americans. Three variants in African Americans were linked to increased suicide risk — one that impacts circadian rhythm, another that is involved in the breakdown of the protein tyrosine, which is a precursor of the dopamine neurotransmitter, and a third that is of unknown function.
They then compared these results to similar large analyses of those who suffer from major depressive disorder.
“From comparison of our suicide data with previous depression data, we found significant genetic overlap between suicide and depression,” Gelernter said.
The researchers plan to expand their scope of enquiry by analyzing genetic data being collected by the Veteran Affairs Million Veterans Program. The VA has made a major push to reduce suicide rates among veterans.
Source: Bill Hathaway – Yale
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Original Research: Open access research for “Genetic associations with suicide attempt severity and genetic overlap with major depression” by Daniel F. Levey, Renato Polimanti, Zhongshan Cheng, Hang Zhou, Yaira Z. Nuñez, Sonia Jain, Feng He, Xiaoying Sun, Robert J. Ursano, Ronald C. Kessler, Jordan W. Smoller, Murray B. Stein, Henry R. Kranzler & Joel Gelernter in Translational Psychiatry. Published January 17 2019.
Genetic associations with suicide attempt severity and genetic overlap with major depression
In 2015, ~800,000 people died by suicide worldwide. For every death by suicide there are as many as 25 suicide attempts, which can result in serious injury even when not fatal. Despite this large impact on morbidity and mortality, the genetic influences on suicide attempt are poorly understood. We performed a genome-wide association study (GWAS) of severity of suicide attempts to investigate genetic influences. A discovery GWAS was performed in Yale-Penn sample cohorts of European Americans (EAs, n = 2,439) and African Americans (AAs, n = 3,881). We found one genome-wide significant (GWS) signal in EAs near the gene LDHB (rs1677091, p = 1.07 × 10−8) and three GWS associations in AAs: ARNTL2 on chromosome 12 (rs683813, p = 2.07 × 10−8), FAH on chromosome 15 (rs72740082, p = 2.36 × 10−8), and on chromosome 18 (rs11876255, p = 4.61 × 10−8) in the Yale-Penn discovery sample. We conducted a limited replication analysis in the completely independent Army-STARRS cohorts. rs1677091 replicated in Latinos (LAT, p = 6.52 × 10−3). A variant in LD with FAH rs72740082 (rs72740088; r2 = 0.68) was replicated in AAs (STARRS AA p = 5.23 × 10−3; AA meta, 1.51 × 10−9). When combined for a trans-population meta-analysis, the final sample size included n = 20,153 individuals. Finally, we found significant genetic overlap with major depressive disorder (MDD) using polygenic risk scores from a large GWAS (r2 = 0.007, p = 6.42 × 10−5). To our knowledge, this is the first GWAS of suicide attempt severity. We identified GWS associations near genes involved in anaerobic energy production (LDHB), circadian clock regulation (ARNTL2), and catabolism of tyrosine (FAH). These findings provide evidence of genetic risk factors for suicide attempt severity, providing new information regarding the molecular mechanisms involved.