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. 2015 Jul 1:179:1-5.
doi: 10.1016/j.jad.2015.02.029. Epub 2015 Mar 10.

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

Amit Anand  1 , Daniel L Koller  2 , William B Lawson  3 , Elliot S Gershon  4 , John I Nurnberger  5 ; BiGS Collaborative
Collaborators, Affiliations

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

Amit Anand et al. J Affect Disord. .

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.

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Conflict of interest statement

Conflict of interest

The authors report no conflict of interest.

Figures

Fig. 1
Fig. 1
Distributions of (a) childhood traumatic event count, 0 to 8 events per subject as measured by Childhood Life Events Scale (CLES); and (b) bipolar disorder age of onset, in the combined GAIN (Genetic Association Information Network for Bipolar Disorder) and TGEN (Translational Genomics Institute) case cohorts; total N = 1119.
Fig. 2
Fig. 2
Mean values of age at onset (AAO, years) by number of childhood traumatic events from the Childhood Life Events Scale (CLES). N = 1119 subjects in the study, all AAO ≥ 12. Error bars indicate standard error of the mean for each CLES level. Results of one-way ANOVA analysis are shown.
See this image and copyright information in PMC

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