Format

Send to

Choose Destination
Mol Neuropsychiatry. 2017 Jul;3(1):1-11. doi: 10.1159/000454773. Epub 2017 Jan 18.

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

Author information

1
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
2
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
3
Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
4
Department of Biomedical Engineering, Institute for Computational Medicine, Johns Hopkins University, Maryland, USA.
5
Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

Abstract

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.

KEYWORDS:

Bipolar disorder; Case/control; Exome; Pathway; Sequencing; Suicidal behavior; Suicide

Supplemental Content

Full text links

Icon for S. Karger AG, Basel, Switzerland Icon for PubMed Central
Loading ...
Support Center