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Abstract: TH-OR32

Epistatic Interactions of APOL1 Modify the Association Between APOL1 and CKD in African and Hispanic Americans

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Vy, Thi ha my, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Chan, Lili, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Do, Ron, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

Chronic kidney disease (CKD) is a major public health problem, and disproportionately effects racial and ethnic minorities. While the Apolipoprotein L1 (APOL1) locus has been identified as a significant genetic contributor to the disparities, only a minority of individuals with APOL1 high-risk genotype develop kidney disease suggesting a major role for genetic and environmental modifiers. Prior genetic association studies studying gene/genetic variants interacting with APOL1 were limited by small sample sizes and detected very few significant interactions.

Methods

In this study, we conducted a genome-wide single nucleotide polymorphism (SNP)xAPOL1 interaction analysis to identify SNPs that modify the association of APOL1 high-risk genotypes with CKD in the largest minority cohort to date. Interaction analyses were conducted separately for four independent cohorts, 12,145 African Americans (AAs) and 16,580 Hispanic Americans (HAs) from the Population Architecture through Genomics and Environment (PAGE) Study and 6,827 AAs and 10,314 HAs from the BioMe Biobank, followed by sample size based meta-analysis.

Results

Among the four cohorts, CKD cases and APOL1 high-risk genotypes were observed with higher frequencies in AA (8.48% CKD and 11.99% APOL1 in PAGE; 18.21% CKD and 13.90% APOL1 in BioMe) than in HA (3.40% CKD and 0.45% APOL1 in PAGE; 14.14% CKD and 1.69% APOL1 in BioMe). We tested about 28 million SNPs in our interaction analyses and identified 51 significant SNPs (P value < 1.0 x 10-6) interacting with the APOL1 locus across the genome (Figure 1). Of these, 28 SNPs were within a gene, and 14 out of the 28 SNPs were within the gene PAIP2B which has been showed to be involved in controlling translation and glucose homeostasis.

Conclusion

Although further biological validation is needed, our results provide early insights on the impact of genetic interaction on the association between APOL1 and kidney disease.

Manhattan Plot of the results from the meta-analysis of SNPxAPOL1 interaction