Assessment of Whole-Exome Sequence Data in Attempted Suicide within a Bipolar Disorder Cohort.
Assessment of Whole-Exome Sequence Data in Attempted Suicide within a Bipolar Disorder Cohort.
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DOI：
10.1159/000454773
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发表时间：
2017-07-01
期刊：
影响因子：
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通讯作者：
Willour, Virginia L
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文献类型：
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作者：
Monson, Eric T;Pirooznia, Mehdi;Willour, Virginia L
自杀行为是一种复杂和破坏性的表型，具有遗传成分，现有的常见遗传变异分析还没有完全解释这一点。这项研究是第一个大规模DNA测序项目，旨在评估罕见的功能性遗传变异在自杀行为风险中的作用。为此，为387名有自杀未遂史的双相情感障碍受试者和631名无自杀未遂经历的双相情感障碍受试者生成了19,000个基因的完整外显子组测序数据。评估了所有外显子组基因中罕见的功能变异，以及被假设为导致自杀行为风险的途径。没有一个结果在保守的Bonferroni校正中幸存下来，尽管已经出现了许多值得额外关注的提示性发现。此外，名义上支持过去的相关基因，如脑源性神经营养因子，和通路，如下丘脑-垂体-肾上腺轴，也被观察到。最后，确定了一条由乙醛脱氢酶基因驱动的新途径。最终，这项调查探索了自杀行为方面的现有努力基本上没有触及的变异，为未来的调查提供了丰富的新信息，例如荟萃分析。
Suicidal behavior is a complex and devastating phenotype with a heritable component that has not been fully explained by existing common genetic variant analyses. This study represents the first large-scale DNA sequencing project designed to assess the role of rare functional genetic variation in suicidal behavior risk. To accomplish this, whole-exome sequencing data for 19,000 genes were generated for 387 bipolar disorder subjects with a history of suicide attempt and 631 bipolar disorder subjects with no prior suicide attempts. Rare functional variants were assessed in all exome genes as well as pathways hypothesized to contribute to suicidal behavior risk. No result survived conservative Bonferroni correction, though many suggestive findings have arisen that merit additional attention. In addition, nominal support for past associations in genes, such as BDNF, and pathways, such as the hypothalamic-pituitary-adrenal axis, was also observed. Finally, a novel pathway was identified that is driven by aldehyde dehydrogenase genes. Ultimately, this investigation explores variation left largely untouched by existing efforts in suicidal behavior, providing a wealth of novel information to add to future investigations, such as meta-analyses.