Genetic Risk for Major Depression Increases Suicidality Across Psychiatric Disorders

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Genetic liability for major depression increases the risk for suicide attempts in major depressive disorder, bipolar disorder, and schizophrenia.

Genetic liability for major depression increases the risk for suicide attempt in major depressive disorder, bipolar disorder, and schizophrenia, according to genome-wide association study results published in the America Journal of Psychiatry in Advance.

Niamh Mullins, PhD, of the Social Genetic and Developmental Psychiatry Centre, King’s College London, United Kingdom, and colleagues genotyped samples from people who had attempted suicide and a control group, all of whom had a specific psychiatric disorder: major depressive disorder (n=1622 and n=8786, respectively), bipolar disorder (n=3264 and n=5500, respectively), and schizophrenia (n=1683 attempters and n=2946, respectively). They then conducted a meta-analysis across disorders, using polygenic risk scoring to explore the genetic relationship between suicide attempt and the psychiatric disorders and employing a within-case analysis strategy.

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The investigators found three genome-wide significant loci for suicide attempts — one associated with suicide attempt in major depressive disorder, one in bipolar disorder, and one in the meta-analysis of suicide attempts in mood disorders. However, no significant association was found in the meta-analysis of all three disorders. In addition, polygenic risk scores for major depression showed a significant association with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).

There were a number of study limitations, including that the study population included only Europeans and that there was a lack of information on the number of suicide attempts, medical consequences, and medication history for all participants. Furthermore, some of the patients who had not attempted suicide at the time of the study may have done so later.

The investigators noted that the goal of suicide-focused genetic studies is to use statistical associations to determine biologic mechanisms and ultimately to develop treatments and preventions.


Several authors reported ties to drug companies. See source for complete information.


Mullins N, Bigdeli TB, Borglum AD, et al. GWAS of suicide attempt in psychiatric disorders and association with major depression polygenic risk scores. AJP in Advance. 2019. doi:10.1176/appi.ajp.201918080957.