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: Thi...

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Main Authors: Kullaya Takkavatakarn, Dinushika Mohottige, Alexander W. Charney, Carol Horowitz, Andrew G. Rundle, Lili Chan, Girish N. Nadkarni
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024925001044
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author Kullaya Takkavatakarn
Dinushika Mohottige
Alexander W. Charney
Carol Horowitz
Andrew G. Rundle
Lili Chan
Girish N. Nadkarni
author_facet Kullaya Takkavatakarn
Dinushika Mohottige
Alexander W. Charney
Carol Horowitz
Andrew G. Rundle
Lili Chan
Girish N. Nadkarni
author_sort Kullaya Takkavatakarn
collection DOAJ
description 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]: 1.08; 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 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.
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spelling doaj-art-075bee472a3d466f8e8c9cbfc1379f5e2025-08-20T02:33:35ZengElsevierKidney International Reports2468-02492025-05-011051476148510.1016/j.ekir.2025.02.015Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States CohortKullaya Takkavatakarn0Dinushika Mohottige1Alexander W. Charney2Carol Horowitz3Andrew G. Rundle4Lili Chan5Girish N. Nadkarni6Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Division of Nephrology, Department of Medicine, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandDivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Department of Population Health and Policy, Institute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York, New York, USAThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Population Health and Policy, Institute for Health Equity Research, Icahn School of Medicine at Mount Sinai, New York, New York, USADepartment of Epidemiology, Columbia University Mailman School of Public Health, New York, New York, USADivision of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Division of Data Driven and Digital Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Correspondence: Lili Chan or Girish Nadkarni, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, New York 10029-6574, USA.Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Division of Data Driven and Digital Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Correspondence: Lili Chan or Girish Nadkarni, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L Levy Place, New York, New York 10029-6574, USA.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]: 1.08; 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 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.http://www.sciencedirect.com/science/article/pii/S2468024925001044APOL1gene-environment interactionkidney outcomemedian household incomeneighborhood socioeconomic statuspoverty rate
spellingShingle Kullaya Takkavatakarn
Dinushika Mohottige
Alexander W. Charney
Carol Horowitz
Andrew G. Rundle
Lili Chan
Girish N. Nadkarni
Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States Cohort
Kidney International Reports
APOL1
gene-environment interaction
kidney outcome
median household income
neighborhood socioeconomic status
poverty rate
title Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States Cohort
title_full Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States Cohort
title_fullStr Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States Cohort
title_full_unstemmed Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States Cohort
title_short Interaction Between Apolipoprotein L1 Genetic Risk and Neighborhood Socioeconomic Status for Kidney Outcomes in a United States Cohort
title_sort interaction between apolipoprotein l1 genetic risk and neighborhood socioeconomic status for kidney outcomes in a united states cohort
topic APOL1
gene-environment interaction
kidney outcome
median household income
neighborhood socioeconomic status
poverty rate
url http://www.sciencedirect.com/science/article/pii/S2468024925001044
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