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

INTRODUCTION

Apolipoprotein L1 () 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 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 km radius circle around their primary residence and used a negative binomial regression model to analyze the interaction between 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 high-risk genotypes. Higher poverty was associated with increased kidney risk (adjusted relative risk [aRR]: 1.08; 95% confidence interval [CI]: 1.01-1.17), whereas higher income was protective (aRR: 0.94; 95% CI: 0.89-0.98). Significant interactions were observed between and SES ( < 0.05). Among high-risk 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 genotypes and neighborhood SES on kidney outcomes suggest that genetic risk may influence the impact of neighborhood SES on kidney health. Among individuals with high-risk variants, a higher neighborhood poverty rate was unexpectedly linked to lower risk, whereas higher neighborhood household income was associated with increased risk.