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

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

Culture, inequality, and health: evidence from the MIDUS and MIDJA comparison

This article seeks to forge scientific connections between three overarching themes (culture, inequality, health). Although the influence of cultural context on human experience has gained notable research prominence, it has rarely embraced another large arena of science focused on the influence social hierarchies have on how well and how long people live. That literature is increasingly focused psychosocial factors, working interactively with biological and brain-based mechanisms, to account for why those with low socioeconomic standing have poorer health. Our central question is whether and how these processes might vary by cultural context. We draw on emerging findings from two parallel studies, Midlife in the U.S. and Midlife in Japan, to illustrate the cultural specificity evident in how psychosocial and neurobiological factors are linked with each other as well as how position in social hierarchies matters for psychological experience and biology. We conclude with suggestions for future multidisciplinary research seeking to understand how social hierarchies matter for people’s health, albeit in ways that may possibly differ across cultural contexts

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

<div><p>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 <i>Regulators of G-protein signaling 10</i> (<i>RGS10</i>), 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.</p></div

Top findings from genome-wide gene environment interaction analysis.

<p>Top findings from genome-wide gene environment interaction analysis.</p

Plots of association results (−log₁₀ <i>p</i>) at 10p26 region in the genome-wide gene–environment interaction analysis.

<p>Chromosome position is plotted according to its physical position with reference to the NCBI build 36. Recombination rate as estimated from the JPT and CHB HapMap data is plotted in light blue. Large red diamond: SNP with strongest evidence for association (rs10510057). Strengths of linkage disequilibrium (LD) (r²) with SNP rs10510057 in the plots are shown (dark red indicates stronger LD).</p

The mean scores of depression symptoms measures grouped by rs10510057 genotypes and exposure to stressful events.

<p>(A) CES-D mean scores grouped by genotypes and SRRS scores. (B) K6 mean scores grouped by genotypes and assessments of fear of being unemployed.</p

Demographic characteristics of samples.

<p>Demographic characteristics of samples.</p