Unit for Psychiatric Research, Psychiatry, Aalborg University Hospital, DK-9100 Aalborg, Denmark.
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy.
Genes (Basel). 2021 Sep 23;12(10):1482. doi: 10.3390/genes12101482.
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 ( = 5.977 × 10). 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.
双相情感障碍（BD）中的自杀是一个重要的临床关注点。遗传学可能与已知的临床因素一起塑造个体患 BD 自杀行为的风险。BD 中缺乏一致的复制可能与其多基因成分有关。在本研究中，我们分析了一组 BD 个体（来自 STEP-BD 数据库），以确定与三种不同自杀相关表型相关的遗传变异体：（1）感觉生活没有价值；（2）关于实施暴力自杀的幻想；（3）先前的自杀企图。分析的样本包括 1115 名 BD 个体。没有一个 SNP 达到全基因组显著水平。然而，AOPEP 基因内含子变异 rs2767403 与表型#1 相关，呈趋势性关联（ = 5.977×10）。分子途径分析显示，在所研究的所有表型中，与突触后信号、神经递质传递和神经发育相关的途径均显著富集。此外，NOTCH 信号或γ-氨基丁酸（GABA）能信号与特定的自杀相关表型有关。本研究有助于假设 BD 中自杀行为的遗传结构与整个途径的改变有关，而不是单个基因。特别是，我们的分子途径分析指出了一些特定的分子事件，这些事件可能是该领域进一步研究的重点。
