The Genetics Website Committee Will be Hosting a Q&A and Eric Monson will Present his Research on Wednesday, 11/12/14
Assessment of Whole Exome Sequence Data in Attempted Suicide
In this study, we present the first large-scale sequencing project designed to assess the role of functional genetic variation within the human exome in the risk for suicidal behavior. Our analysis takes advantage of recently-developed variant collapsing methods to determine whether suicide attempters have elevated rates of functional mutational burden as compared to non-attempters. To do this, we generated whole exome sequencing data for 387 bipolar subjects with a history of a moderate or serious suicide attempt and 631 bipolar subjects with no history of suicide attempt. Additional sequencing targets for core regulatory regions of approximately 1500 genes predicted to be involved with synaptic function were also included in the data. Functional variant sets were assessed in groups defined by gene-loci and pathways using mutational burden and sequence kernel association tests. No signals survived correction for multiple testing. Our suggestive findings implicate glutamatergic signaling, as did our previous genome wide association study. This study demonstrates a first look at the potential power behind whole exome sequencing in the investigation of functional coding and regulatory variation contributing to the complex phenotype of suicidal behavior and the promise such techniques might afford as large scale next generation sequencing efforts continue to expand.