Key result
No SNPs reached genome-wide significance for suicide-related phenotypes in bipolar disorder, though rs2767403 showed a trend of association with feeling life was not worth living (p=5.977×10−6).
Why the study?
Suicide in bipolar disorder is a relevant clinical concern and genetics may shape risk, but consistent replication has been lacking, potentially due to a multigenetic component.
Are specific genetic variants or molecular pathways associated with suicide-related phenotypes in individuals with bipolar disorder?
Observational (n=1,115)
Are specific genetic variants or molecular pathways associated with suicide-related phenotypes in individuals with bipolar disorder?
p-value: p=5.977 × 10−6
The genetic architecture of suicide behaviors in bipolar disorder may be driven by alterations in entire molecular pathways, such as neurotransmission and neurodevelopment, rather than single genes.
May link genetic variants to suicide phenotypes in BD; leaves open replication before any risk stratification use.
Suicide in Bipolar Disorder (BD) is a relevant clinical concern. Genetics may shape the individual risk for suicide behavior in BD, together with known clinical factors. The lack of consistent replication in BD may be associated with its multigenetic component. In the present contribution we analyzed a sample of BD individuals (from STEP-BD database) to identify the genetic variants potentially associated with three different suicide-related phenotypes: (1) a feeling that the life was not worth living; (2) fantasies about committing a violent suicide; (3) previous attempted suicide. The sample under analysis included 1115 BD individuals. None of the SNPs reached genome-wide significance. However, a trend of association was evidenced for rs2767403, an intron variant of AOPEP gene, in association with phenotype #1 (p = 5.977 × 10−6). The molecular pathway analysis showed a significant enrichment in all the investigated phenotypes on pathways related to post synaptic signaling, neurotransmission and neurodevelopment. Further, NOTCH signaling or the γ-aminobutyric acid (GABA)-ergic signaling were found to be associated with specific suicide-related phenotypes. The present investigation contributes to the hypothesis that the genetic architecture of suicide behaviors in BD is related to alteration of entire pathways rather than single genes. In particular, our molecular pathway analysis points on some specific molecular events that could be the focus of further research in this field.
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Lybech et al. (2021) conducted an observational in Bipolar Disorder (n=1,115). Genetic variants (SNPs) was evaluated on Association with three suicide-related phenotypes (feeling life not worth living, violent suicide fantasies, previous attempted suicide) (p=5.977 × 10−6). No SNPs reached genome-wide significance for suicide-related phenotypes in bipolar disorder, though rs2767403 showed a trend of association with feeling life was not worth living (p=5.977×10−6).
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