Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients.

Background: A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide.

Methods: We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder (N = 219). We analyzed these variants for a possible association with the suicide severity score (ranging from suicidal ideation/plan to serious suicide attempt) from the Schedule for Clinical Assessment in Neuropsychiatry. We conducted tests of individual variants and gene-based tests.

Results: We found a number of DNA variants in the transforming growth factor beta receptor 1 gene (TGFBR1) to be suggestively associated with suicide severity scores (p < 0.005). The gene-based tests also pointed to TGFBR1 to be associated with suicide severity (p = 0.0001). However, these findings were not replicated in an independent bipolar disorder sample.

Conclusions: We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.