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Abstract：
Suicidal behavior has been shown to have a heritable component that is partly driven by psychiatric disorders [Brent and Mann, 2005]. However, there is also an independent factor contributing to the heritability of suicidal behavior. We previously conducted a genome-wide association study (GWAS) of bipolar suicide attempters and bipolar non-attempters to assess this independent factor [Willour et al., 2012]. This GWAS implicated glutamatergic neurotransmission in attempted suicide. In the current study, we have conducted a targeted next-generation sequencing study of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, neurexin, and neuroligin gene families in 476 bipolar suicide attempters and 473 bipolar non-attempters. The goal of this study was to gather sequence information from coding and regulatory regions of these glutamatergic genes to identify variants associated with attempted suicide. We identified 186 coding variants and 4,298 regulatory variants predicted to be functional in these genes. No individual variants were overrepresented in cases or controls to a degree that was statistically significant after correction for multiple testing. Additionally, none of the gene-level results were statistically significant following correction. While this study provides no direct support for a role of the examined glutamatergic candidate genes, further sequencing in expanded gene sets and datasets will be required to ultimately determine whether genetic variation in glutamatergic signaling influences suicidal behavior. © 2016 Wiley Periodicals, Inc.
摘要：
自杀行为已被证明具有可遗传的成分，部分是由精神疾病引起的[Brent和Mann，2005].然而,自杀行为的遗传性也有一个独立的因素。我们先前对双相型自杀未遂者和双相型非自杀未遂者进行了全基因组关联研究（GWAS），以评估这一独立因素[Willour等人。,2012].该GWAS与企图自杀中的谷氨酸能神经传递有关。在目前的研究中,我们对谷氨酸能N-甲基-D-天冬氨酸（NMDA）受体进行了靶向的下一代测序研究，Neurexin,476例双极性自杀未遂者和473例双极性非自杀未遂者中的Neuroligin基因家族。这项研究的目的是从这些谷氨酸能基因的编码和调节区域收集序列信息，以鉴定与企图自杀相关的变异。我们鉴定了186个编码变体和4,298个预测在这些基因中有功能的调节变体。在病例或对照中,在校正多重测试后,没有单个变体在统计学上显著的程度上被过多地呈现。此外,校正后的基因水平结果均无统计学意义.虽然这项研究没有直接支持所检查的谷氨酸能候选基因的作用，需要对扩展的基因集和数据集进行进一步测序,以最终确定谷氨酸能信号的遗传变异是否会影响自杀行为.©2016威利期刊，Inc.
