Genetic and childhood trauma interaction effect on age of onset in bipolar disorder: An exploratory analysis

Abstract

Introduction: This study investigated whether early life trauma mediates genetic effects on the age at onset (AAO) of bipolar disorder.

Method: Data from the BiGS Consortium case samples (N=1119) were used. Childhood traumatic events were documented using the Childhood Life Events Scale (CLES). Interaction between occurrence of childhood trauma and common genetic variants throughout the genome was tested to identify single nucleotide polymorphic gene variants (SNPs) whose effects on bipolar AAO differ between individuals clearly exposed (CLES≥2) and not exposed (CLES=0) to childhood trauma.

Results: The modal response to the CLES was 0 (N=480), but an additional 276 subjects had CLES=1, and 363 subjects reported 2 or more traumatic lifetime events. The distribution of age at onset showed a broad peak between ages 12 and 18, with the majority of subjects having onset during that period, and a significant decrease in age of onset with the number of traumatic events. No single SNP showed a statistically significant interaction with the presence of traumatic events to impact bipolar age at onset. However, SNPs in or near genes coding for calcium channel activity-related proteins (Gene Ontology: 0005262) were found to be more likely than other SNPs to show evidence of interaction using the INRICH method (p<0.001).

Limitations: Retrospective ascertainment of trauma and AAO.

Conclusion: Interaction effects of early life trauma with genotype may have a significant effect on the development and manifestation of bipolar disorder. These effects may be mediated in part by genes involved in calcium signaling.

Keywords: Age of onset; Bipolar disorder; Calcium; Childhood trauma; GWAS; Genetic.