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Genetic liability for MDD boosts risk for suicide attempt across psychiatric disorders

Genetic liability for major depressive disorder increased the risk for suicide attempt in patients with major depressive disorder, bipolar disorder and schizophrenia, according to results from a large genome-wide association study published in American Journal of Psychiatry.

"Like many psychiatric disorders, suicide attempt is known to have a partially genetic underpinning and genetic studies can provide invaluable insights into the underlying biology," Niamh Mullins, PhD, from the Social Genetic and Developmental Psychiatry Centre at King’s College London and the department of genetics and genomic sciences at Icahn School of Medicine at Mount Sinai, said in a press release.

To shed light on the genetic etiology of suicide attempt, researchers conducted the largest genome-wide association study (GWAS) to date using cohorts of individuals with MDD, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium. They compared participants who attempted suicide with those who did not for each disorder, then conducted a meta-analysis across disorders. Using polygenic risk scoring, they examined the genetic relationship between suicide attempt and the psychiatric disorders.

The study included: 1,622 individuals who attempted suicide and 8,786 who did not with MDD; 3,264 individuals who attempted suicide and 5,500 who did not with bipolar disorder; and 1,683 individuals who attempted suicide and 2,946 who did not with schizophrenia.

The proportion of participants reporting suicide attempt ranged from 16% in major depression to 36% to 37% in bipolar disorder and schizophrenia. Analysis yielded three genome-wide significant loci for suicide attempt:

• one relating to suicide attempt in MD;
• one relating to suicide attempt in bipolar disorder; and
• one in the meta-analysis of suicide attempt in mood disorders.

These connections were not replicated independent mood disorder cohorts from the U.K. Biobank and iPSYCH, according to the study. In addition, the researchers observed no significant associations in the meta-analysis of all three disorders.

The results also showed that polygenic risk scores for MDD were significantly linked to suicide attempt in all psychiatric disorders (MDD: R² = 0.25%; bipolar disorder: R² = 0.24%; schizophrenia: R² = 0.40%).

"These results indicate the existence of a shared genetic etiology between suicide attempt and major depression that is common to suicide attempt in different psychiatric disorders," Mullins said in the release.

"Our study is the first consortium-based GWAS on suicide attempt and makes significant progress in increasing numbers by combining samples across clinical cohorts,” she continued. “However, further collaborative efforts to amass samples on an even larger scale will be essential to identify specific genetic variants which play a role in increasing risk of suicide attempt." – by Savannah Demko

Disclosure: Mullins report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.