Abstract: SA-PO069
Genetic Ancestry as a Predictor of Kidney Transplant Outcomes
Session Information
- Transplantation: Recipient and Donor Assessment
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1802 Transplantation: Clinical
Authors
- Neugut, Y. Dana, Columbia University Medical Center, New York, New York, United States
- Liu, Lili, Columbia University Medical Center, New York, New York, United States
- Zhang, Junying, Columbia University Medical Center, New York, New York, United States
- Fasel, David, Columbia University Medical Center, New York, New York, United States
- Mehl, Karla, Columbia University Medical Center, New York, New York, United States
- Wold, Jaclyn L., Columbia University Medical Center, New York, New York, United States
- Ozay, Fatih, Columbia University Medical Center, New York, New York, United States
- Balderes, Olivia, Columbia University Medical Center, New York, New York, United States
- Mohan, Sumit, Columbia University Medical Center, New York, New York, United States
- Radhakrishnan, Jai, Columbia University Medical Center, New York, New York, United States
- Ratner, Lloyd E., Columbia University Medical Center, New York, New York, United States
- Cohen, David J., Columbia University Medical Center, New York, New York, United States
- Gharavi, Ali G., Columbia University Medical Center, New York, New York, United States
- Kiryluk, Krzysztof, Columbia University Medical Center, New York, New York, United States
Background
African-American (AA) kidney recipients have higher rates of allograft rejection and failure. However, it is unknown to what extent the inferior outcomes in self-reported AA’s are due to genetic effects or confounding by socioeconomic status (SES). In this study, we test the effects of recipient African admixture, a quantitative measure of genetic ancestry derived from genome-wide SNP data, in multivariable models adjusted for SES factors.
Methods
Our study used a multiethnic retrospective single center cohort of 1,083 kidney allograft recipients, including 206 self-reported AA’s. Subjects were genotyped with high resolution SNP arrays (MEGA chip, Illumina); African admixture proportions were derived using ADMIXTURE software. All subjects were geo-coded and U.S. census tract variables were used as proxies of SES. Multivariable Cox models were constructed to predict time to biopsy-proven rejection and time to death-censored allograft failure, and race-related variables of interest were tested in each model.
Results
The cohort median follow-up time was 78.3 months, and included 432 patients with rejection (median 5.9 months) and 193 with failure (median 72.3 months). We confirmed significant impact of recipient’s self-reported AA race (HR 1.47 (95% CI: 1.18-1.83)) and African admixture proportion (HR 1.64 (95% CI: 1.22-2.19)) on acute rejection. Both race-related metrics also had similar effects in the adjusted models of allograft failure (self-report: HR 1.42 (95% CI: 1.02-1.97); admixture: HR 1.48 (95% CI: 0.96-2.29)). Recipient APOL1 risk genotype status, associated with African ancestry and several kidney diseases, did not explain these associations. U.S. census-derived median income and education level did not confound the association between race and either rejection or failure.
Conclusion
Our study is the first to test a genetic measure of recipient African ancestry for inclusion in clinical models of kidney transplant outcomes. Based on our results, self-reported AA race and a genetically-derived continuous measure of African ancestry performed similarly in predicting the risk of allograft rejection and failure, and both predictors were independent after multivariable adjustment for U.S. census-based metrics of SES.
Funding
- NIDDK Support