Assessment of Whole-Exome Sequence Data in Attempted Suicide within a Bipolar Disorder Cohort

Monson, E. T., Pirooznia, M., Parla, J., Kramer, M., Goes, F. S., Gaine, M. E., Gaynor, S. C., de Klerk, K., Jancic, D., Karchin, R., McCombie, W. R., Zandi, P. P., Potash, J. B., Willour, V. L. (July 2017) Assessment of Whole-Exome Sequence Data in Attempted Suicide within a Bipolar Disorder Cohort. Mol Neuropsychiatry, 3 (1). pp. 1-11. ISSN 2296-9209 (Print)2296-9179

DOI: 10.1159/000454773


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 approximately 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.

Item Type: Paper
Uncontrolled Keywords: Bipolar disorder Case/control Exome Pathway Sequencing Suicidal behavior Suicide
Subjects: diseases & disorders > mental disorders
Investigative techniques and equipment > whole exome sequencing
Investigative techniques and equipment > assays > whole exome sequencing
CSHL Authors:
Communities: CSHL labs > McCombie lab
Depositing User: Matt Covey
Date: July 2017
Date Deposited: 08 Sep 2017 19:36
Last Modified: 08 Sep 2017 19:36
PMCID: PMC5582499
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