A targeted sequencing study of glutamatergic candidate genes in suicide attempters with bipolar disorder.
A targeted sequencing study of glutamatergic candidate genes in suicide attempters with bipolar disorder.
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DOI：
10.1002/ajmg.b.32479
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Willour VL
中科院分区：
文献类型：
--
作者：
Gaynor SC;Breen ME;Monson ET;de Klerk K;Parsons M;DeLuca AP;Scheetz TE;Zandi PP;Potash JB;Willour VL
自杀行为已被证明有一个遗传的组成部分，部分是由精神疾病驱动的。然而，还有一个独立的因素有助于自杀行为的遗传性。我们之前对双相自杀倾向者和双相非自杀倾向者进行了全外显子组测序研究，以评估这一独立因素。整个外显子组的研究表明，自杀未遂中存在多巴胺能神经传递，我们对自杀未遂表型的全基因组关联研究（GWAS）也是如此。在本研究中，我们对476名双相自杀患者和473名双相非自杀患者的NMDA受体、neurexin和neuroligin基因家族进行了有针对性的下一代测序研究。本研究的目的是从这些神经元能基因的编码和调控区域收集序列信息，以识别与自杀未遂相关的变异。我们确定了186个编码变体和4，298个调控变体，预测这些基因中有功能。在多重检验校正后，病例或对照组中没有个体变异的过度表达达到统计学显著性的程度。此外，校正后，基因水平结果均无统计学显著性。虽然这项研究没有提供直接支持的作用，所检查的amatergic候选基因，进一步测序扩展的基因集和数据集将需要最终确定amatergic信号的遗传变异是否影响自杀行为。
Suicidal behavior has been shown to have a heritable component that is partly driven by psychiatric disorders. However, there is also an independent factor contributing to the heritability of suicidal behavior. We previously conducted a whole exome sequencing study of bipolar suicide attempters and bipolar non-attempters to assess this independent factor. This whole exome study implicated glutamatergic neurotransmission in attempted suicide, as did our genome-wide association study (GWAS) of the attempted suicide phenotype. 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.
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影响因子：
5.8
作者：
Barnett, Derek W.;Garrison, Erik K.;Marth, Gabor T.
通讯作者：
Marth, Gabor T.
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Gauthier J;Siddiqui TJ;Huashan P;Yokomaku D;Hamdan FF;Champagne N;Lapointe M;Spiegelman D;Noreau A;Lafrenière RG;Fathalli F;Joober R;Krebs MO;DeLisi LE;Mottron L;Fombonne E;Michaud JL;Drapeau P;Carbonetto S;Craig AM;Rouleau GA
通讯作者：
Rouleau GA
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M