title: Genetic and childhood trauma interaction effect on age of onset in bipolar disorder: An exploratory analysis.
abstract: BACKGROUND
  This study investigated whether early life trauma mediates genetic effects on the age at onset (AAO) of bipolar disorder.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  Retrospective ascertainment of trauma and AAO.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Behavioral Health, Cleveland Clinic, 9500 Euclid Avenue/P57, Cleveland, OH 44195 United States; Department of Psychiatry, Indiana University School of Medicine, United States. Electronic address: ananda@ccf.org.
authors.forename: Amit
authors.initials: A
authors.lastname: Anand
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.affiliation: Department of Psychiatry, Howard University, United States.
authors.forename: William B
authors.initials: WB
authors.lastname: Lawson
authors.affiliation: Department of Psychiatry, University of Chicago, United States.
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, United States; Department of Medical and Molecular Genetics, Indiana University School of Medicine, United States; Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, United States.
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
mesh_terms: D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D017677:Age Distribution; D017668:Age of Onset; D001714:Bipolar Disorder / Q000150:complications* / Q000235:genetics* / Q000523:psychology; D015220:Calcium Channels / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000067073:Psychological Trauma / Q000150:complications* / Q000235:genetics* / Q000523:psychology; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States
chemical_list: D015220:Calcium Channels
keywords: Age of onset; Bipolar disorder; Calcium; Childhood trauma; GWAS; Genetic
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