The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population

PLoS One. 2016 Aug 16;11(8):e0160823. doi: 10.1371/journal.pone.0160823. eCollection 2016.


Stressful events have been identified as a risk factor for depression. Although gene-environment (G × E) interaction in a limited number of candidate genes has been explored, no genome-wide search has been reported. The aim of the present study is to identify genes that influence the association of stressful events with depression. Therefore, we performed a genome-wide G × E interaction analysis in the Japanese population. A genome-wide screen with 320 subjects was performed using the Affymetrix Genome-Wide Human Array 6.0. Stressful life events were assessed using the Social Readjustment Rating Scale (SRRS) and depression symptoms were assessed with self-rating questionnaires using the Center for Epidemiologic Studies Depression (CES-D) scale. The p values for interactions between single nucleotide polymorphisms (SNPs) and stressful events were calculated using the linear regression model adjusted for sex and age. After quality control of genotype data, a total of 534,848 SNPs on autosomal chromosomes were further analyzed. Although none surpassed the level of the genome-wide significance, a marginal significant association of interaction between SRRS and rs10510057 with depression were found (p = 4.5 × 10-8). The SNP is located on 10q26 near Regulators of G-protein signaling 10 (RGS10), which encodes a regulatory molecule involved in stress response. When we investigated a similar G × E interaction between depression (K6 scale) and work-related stress in an independent sample (n = 439), a significant G × E effect on depression was observed (p = 0.015). Our findings suggest that rs10510057, interacting with stressors, may be involved in depression risk. Incorporating G × E interaction into GWAS can contribute to find susceptibility locus that are potentially missed by conventional GWAS.

MeSH terms

  • Adult
  • Depression / complications
  • Depression / genetics*
  • Female
  • Gene-Environment Interaction*
  • Genome-Wide Association Study*
  • Humans
  • Japan
  • Male
  • Pilot Projects
  • Polymorphism, Single Nucleotide
  • Stress, Psychological / complications

Grant support

This work was supported by the Grants-in-Aid for Scientific Research on Priority Areas “Comprehensive Genomics” and “Applied Genomics” (T. Sasaki received No. 17019029 and No. 21300242; TO received No. 25461723) and for Scientific Research on Innovative Areas; “Elucidation of social stratification mechanism and control over health inequality in contemporary Japan: New interdisciplinary area of social and health sciences” (The Project “Social Stratification and Health”: AT and NK received No. 21119002) from the Ministry of Education, Science, Sports and Culture of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.