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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, Pdiscovery = 7.68 × 10−14, Preplication = 1.96 × 10−2) and rs150451424 at 16p13.3 (RBFOX1, Pdiscovery = 1.89 × 10−10, Preplication = 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. [ABSTRACT FROM AUTHOR]

The abnormal timing of pubertal development is a risk factor for addictive disorders among adolescents. However, whether the precocious or late puberty has influence on addiction in adults remains unclear. Based on the data of 336,398 European participants in the UK Biobank, we explored the associations between secondary sexual characteristics (SSCs) outset time abnormality and addiction with observational analyses. Linkage disequilibrium score regression (LDSC) was conducted to test for the genetic correlation between them. For significant genetic associations, two-sample Mendelian randomization (MR) analyses were further performed for causal inferences. The genetic instruments were derived from genome-wide association studies of early menarche (N = 165,862), late first facial hair grows (N = 141,210) and late voice broke (N = 138,461). Observational analyses detected several significant associations between SSCs outset time abnormality and addiction, such as early menarche vs addiction to any substance or behavior (OR = 1.37, PFDR = 3.31 × 10−4) and late first facial hair grows vs alcohol addiction (OR = 1.24, PFDR = 2.40 × 10−15). MR analyses found genetically predicted early menarche was causally associated with higher risk of tobacco addiction (OR = 1.35, 95% CI: 1.15–1.58, PIVW = 0.0002) and addiction to any substance or behavior (OR = 1.39, 95% CI: 1.12–1.73, PIVW = 0.003). Our findings suggest the prevention and treatment for precocious puberty might be protective factors for addiction in female adults. Early preventive interventions for addictive behaviors are needed for females at high risk. [ABSTRACT FROM AUTHOR]