Socioeconomic deprivation and atrial fibrillation risk: an observational and gene-environment interaction analysis

Abstract Background The association between socioeconomic deprivation and incident atrial fibrillation (AF) is debated, along with limited evidence on how genetic predisposition to AF interacts with socioeconomic deprivation and AF risk. Purpose To evaluate the association and gene-environmental interaction between socioeconomic deprivation and the risk of incident AF. Methods From the UK Biobank prospective cohort, we selected participants who were free from previous AF. Participants with missing values and those who did not pass the genetic quality control were excluded. As an indicator of socioeconomic deprivation, we utilised the indices of multiple deprivation (IMD), which is calculated from scores of multiple socioeconomic factors, including crime, education, employment, health, housing, income, and living environment. Participants were divided into 3 groups by IMD; the top 20% as high IMD (most deprived), the bottom 20% as low IMD, and 20-80% as mid IMD. Using a polygenic risk score (PRS) for AF generated using a Bayesian approach applied to external genome-wide association study data, the interaction between genetic risk and socioeconomic deprivation was assessed. The primary endpoint was incident AF during a median of 13.7 years of follow-up. Results A total of 377,386 (aged 56.5±8.1 years, 45.2% male) were analysed. The high IMD group (n=85,108) was younger and had a higher proportion of comorbidities than the mid or low-IMD groups. An increase in IMD as a continuous variable was significantly associated with an increased risk of incident AF. The high IMD group showed a significantly increased risk of AF (multivariable-adjusted hazard ratio [aHR]=1.12, 95% confidence interval=1.07-1.17, P<0.001) compared with the low IMD group (incidence rate 7.7 vs. 4.8/1,000 person-year). All components of IMD except housing score significantly increased the risk of incident AF (aHR ranged from 1.07 to 1.15). Within each IMD group, higher AF PRS groups were significantly associated with an increased risk of incident AF with the low AF PRS group as a reference, showing aHRs of 1.50 for mid-PRS and 2.57 for high-PRS in the low IMD group, 1.60 and 2.65 in the mid-IMD group, and 1.55 and 2.33 in the high IMD group, respectively (all P<0.001). The impact of socioeconomic deprivation was attenuated in participants with high AF PRS (P for interaction=0.042), mainly driven by the interaction effect of crime (P for interaction [Pi]=0.005), employment deprivation (Pi=0.005), and health deprivation scores (Pi=0.043). Conclusion Socioeconomically deprived individuals had a significantly higher risk of AF, and the effect was partially modified by genetic predisposition to AF. A personalised approach to applying AF screening for high-risk individuals may be more efficacious. Legal measures and policies to enhance public health by alleviating socioeconomic inequalities are needed to mitigate AF risk and improve cardiovascular health outcomes.