Gene-by-social-environment interaction (GxSE) between ADCYAP1R1 genotype and neighborhood crime predicts major depression symptoms in trauma-exposed women

Sarah R. Lowe, John Pothen, James W. Quinn, Andrew Rundle, Bekh Bradley, Sandro Galea, Kerry J. Ressler, Karestan C. Koenen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Background Few studies have explored interactions between genes and social environmental exposures (GxSEs) for trauma-related psychopathology, including symptoms of posttraumatic stress (PTS) and major depression (MD). The extant literature suggests the possibility of a GxSE between the rs2267735 variant of the ADCYAP1R1 gene and neighborhood crime. The current study aimed to explore this possibility among a predominantly African American sample of trauma-exposed women. Methods Female participants (N=1361) were recruited from a public hospital, and completed measures of PTS and MD symptoms and provided DNA samples. Participants' home addresses were mapped onto 300 neighborhoods (2010 census tracts), and data on crime within neighborhoods was collected. Results Multilevel models detected a significant GxSE between rs2267735 and neighborhood crime for MD symptoms (p=.01). Having two copies of the risk (C) allele was associated with higher MD symptoms for participants living in high-crime neighborhoods. Limitations At least six limitations are noteworthy: (1) low statistical power; (2) use of self-report symptom inventories; (3) lack of information on symptom onset; (4) homogeneous sample from a single metropolitan area; (5) non-specific index of crime; and (6) use of census tracts to define neighborhoods. Conclusions The results provide further evidence of GxSEs for psychiatric outcomes among trauma-exposed populations. Further investigations of genetic factors for trauma-related psychopathology should include careful assessments of the social environment.

Original languageEnglish
Pages (from-to)147-150
Number of pages4
JournalJournal of Affective Disorders
StatePublished - 15 Nov 2015


  • Gene-by-social-environment interactions
  • Genetic risk
  • Major depression
  • Multilevel modeling
  • Neighborhood crime
  • Posttraumatic stress
  • Social environment


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