title: The First Pilot Genome-Wide Gene-Environment Study of Depression in the Japanese Population.
abstract: 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.
authors.affiliation: Graduate School of Clinical Psychology, Teikyo Heisei University Major of Professional Clinical Psychology, Tokyo, Japan.|Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Otowa
authors.affiliation: Department of Psychiatry, Shonan Kamakura General Hospital, Kanagawa, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawamura
authors.affiliation: Department of Public Health, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors.forename: Akizumi
authors.initials: A
authors.lastname: Tsutsumi
authors.affiliation: Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Norito
authors.initials: N
authors.lastname: Kawakami
authors.affiliation: Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Chiemi
authors.initials: C
authors.lastname: Kan
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Umekage
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Laboratory of Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D003863:Depression / Q000150:complications / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008297:Male; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D013315:Stress, Psychological / Q000150:complications