Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States Cohort

Introduction: Apolipoprotein L1 (APOL1) risk alleles G1 and G2, confer a higher risk of kidney outcomes but are influenced by other genetic and environmental factors. The interaction between neighborhood socioeconomic status (SES) and APOL1 associated risk of kidney outcomes is unknown. Methods: This retrospective study included self-reported Black individuals with genetic, clinical, and residential data. We defined the neighborhood as a 1 km2 radius circle around their primary residence and used a negative binomial regression model to analyze the interaction between APOL1 variants and neighborhood SES, specifically poverty rate and median household income, for a composite kidney outcome of a sustained 30% estimated glomerular filtration rate (eGFR) decline or end-stage kidney disease (ESKD) over 8 years. Results: Of 4296 participants, 829 (19%) had the composite kidney outcome; 20% with and 9% without the composite outcome had APOL1 high-risk genotypes. Higher poverty was associated with increased kidney risk (adjusted relative risk [aRR]: 1.10; 95% confidence interval [CI]: 1.02–1.18), whereas higher income was protective (aRR: 0.95; 95% CI: 0.91–0.98). Significant interactions were observed between APOL1 and SES (P < 0.05). Among high-risk APOL1 individuals, higher poverty was linked to lower risk (aRR: 0.86; 95% CI: 0.43–2.75), whereas higher income increased the risk (aRR: 1.07; 95% CI: 0.51–2.13). Conclusion: Significant interactions between APOL1 genotypes and neighborhood SES on kidney outcomes suggest that APOL1 genetic risk may influence the impact of neighborhood SES on kidney health. Among individuals with APOL1 high-risk variants, a higher neighborhood poverty rate was unexpectedly linked to lower risk, whereas higher neighborhood household income was associated with increased risk.

Duke Scholars

Author Dinushika Mohottige Medicine, Nephrology