Interaction of disease-associated genetic variants by socioeconomic status: Is there potential to explore socioeconomic inequalities in health?

Background: The concept of gene by environment interaction (G × E) has been extensively discussed in the sociological literature, but how it might contribute to the exploration of socioeconomic inequalities in health has hardly been evaluated so far. By regarding the incorporation of G × E in the explanation of health inequalities it is hypothesized that the effects of genetic variants on disease may be not of the same size or direction across socioeconomic groups, but modified by socioeconomic status (SES) and its related conditions such as diet, physical activity or exposure to environmental pollutants. Twin studies already suggest that disease variance explained by genetic factors is decreasing with higher SES levels. The aim of our study was (1) to evaluate the empirical evidence for G × SES interaction on health outcomes by focusing on recent genetic findings for common complex diseases and (2) to exemplify the concept of G × SES interaction by exploring effect modifications of a 9p21 genetic variant – which has been shown to be robustly associated with cardiovascular disease (CVD) in different study populations – by indicators of SES. Methods: (1) Literature research was conducted to identify empirical studies which have explored G × SES interactions for health outcomes. (2) In 4,116 participants of the Heinz Nixdorf Recall Study the genetic effect of a 9p21 genetic variant on incident CVD was analyzed by including G × SES interaction terms as well as stratified analyses of the genetic effect by SES (separately for education and income) using sex- and age-adjusted multiple regression models to calculate hazard ratios (HR) and their respective 95% confidence intervals (95%-CI). Results: (1) Published study results reporting G × SES interactions with regard to recent genetic findings for common complex diseases are sparse, but studies have been identified which have explored genetic variants and their modification by environmental factors such as dietary intake and smoking status that have been shown to be related to SES in different study populations. (2) In the exemplary analyses of the genetic effect of the 9p21 variant on CVD a significant G × SES interaction was observed using income as SES indicator (pG × SES = 0.04 with a HR of 1.60 [95%-CI: 1.22, 2.10] for the lowest and a HR of 0.95 [95%-CI: 0.64, 1.42] for the highest income quartile), but not for using education as SES indicator. Discussion: There is a lack of studies exploring G × SES interactions for genetic variants of common complex diseases, but the overall idea that genetic factors do not operate independently of an individual's environment seems to be plausible and has the potential to contribute to the exploration of health inequalities. It represents a more likely approach to examine how the (social) environment „get under the skin” to produce social inequalities in health rather than assuming putative differences in the distribution of disease-related genetic variants across SES groups. As the exemplary analyses have shown, the effect of a 9p21 variant on CVD appears to be modified by income in a population-based cohort. This supports the hypothesis that better material conditions enable higher SES groups to reduce their genetic susceptibility to disease.