The Comprehensive Effect of Socioeconomic Deprivation on Smoking Behavior: an Observational and Genome-Wide by Environment Interaction Analyses in UK Biobank

Smoking has caused great public health burdens in the global. Although socioeconomic factors have been confirmed to substantially influence smoking behaviors, the impact of comprehensive social deprivations on smoking behavior and related biological mechanisms are still unclear. Supported by UK Biobank cohort, we randomly divided 369,915 participants into discovery cohort (60%) and replication cohort (40%). We first tested the associations for index of multiple deprivation (IMD) and 7 IMD subdomains with ever-smoking and daily smoking frequency using regression models in both cohorts. Genome-wide by environment interaction study (GWEIS) was further conducted by using PLINK2.0 to detect the effects of the interactions between SNPs and IMD subdomains on two smoking behaviors. In discovery and replication cohorts, we observed the more deprivation status the individuals were in, the higher daily smoking frequency or risk to be ever smokers. And among the subdomains of IMD, income, education, health, living environment, and crime deprivation were positively associated with the risk of smoking behaviors, while employment deprivation was negatively correlated with smoking behaviors (all P < 0.0125). Totally, GWEIS analysis detected 23 shared significant socioeconomic-deprivation interacted loci for daily smoking frequency in two cohorts, such as rs116680599 at 2p16.3 ( NRXN1 , P discovery = 7.68 × 10 −14 , P replication = 1.96 × 10 −2 ) and rs150451424 at 16p13.3 ( RBFOX1 , P discovery = 1.89 × 10 −10 , P replication = 1.96 × 10 −2 ) interacting with employment deprivation. We illustrated the diverse effects of IMD on smoking behaviors and provided insights for the biological mechanisms of the interaction effects between socioeconomic deprivation with genetic factors on smoking behaviors.