African ancestry-specific alleles and kidney disease risk in hispanics/latinos

Holly J. Kramer, Adrienne M. Stilp, Cathy C. Laurie, Alex P. Reiner, James Lash, Martha L. Daviglus, Sylvia E. Rosas, Ana C. Ricardo, Bamidele O. Tayo, Michael F. Flessner, Kathleen F. Kerr, Carmen Peralta, Ramon Durazo-Arvizu, Matt Conomos, Timothy Thornton, Jerome Rotter, Kent D. Taylor, Jainwen Cai, John Eckfeldt, Han ChenGeorge Papanicolau, Nora Franceschini

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

African ancestry alleles may contribute to CKD among Hispanics/Latinos, but whether associations differ by Hispanic/Latino background remains unknown. We examined the association of CKD measures with African ancestry-specific APOL1 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit b gene [HBB] variant) on the basis of imputation in 12,226 adultHispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-Tocreatinine ratios.Overall, 41.4%of participantsweremale, 44.6%of participants had aCaribbean background, and the mean age of all participants was 46.1 years. The Caribbean background group, compared with the Mainland background group, had a higher frequency of two APOL1 alleles (1.0% versus 0.1%) and the HBB variant (2.0% versus 0.7%). In the Caribbean background group, presence of APOL1 alleles (2 versus 0/1 copies) or the HBB variant (1 versus 0 copies) were significantly associated with albuminuria (odds ratio [OR], 3.2; 95% confidence interval [95% CI], 1.7 to 6.1; and OR, 2.6; 95% CI, 1.8 to 3.8, respectively) and albuminuria and/or EGFR,60ml/min per 1.73m2 (OR, 2.9; 95%CI, 1.5 to 5.4; andOR, 2.4; 95%CI, 1.7 to 3.5, respectively). The urine albumin-To-creatinine ratio genome-wide association scan identified associations with the HBB variant among all participants, with the strongest association in the Caribbean background group (P=3.1310210 versus P=9.331023 for theMainland background group). In conclusion, African-specific alleles associate with CKD in Hispanics/Latinos, but allele frequency varies by Hispanic/Latino background/ancestry.

Original languageEnglish (US)
Pages (from-to)915-922
Number of pages8
JournalJournal of the American Society of Nephrology
Volume28
Issue number3
DOIs
StatePublished - Mar 2017

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    Kramer, H. J., Stilp, A. M., Laurie, C. C., Reiner, A. P., Lash, J., Daviglus, M. L., Rosas, S. E., Ricardo, A. C., Tayo, B. O., Flessner, M. F., Kerr, K. F., Peralta, C., Durazo-Arvizu, R., Conomos, M., Thornton, T., Rotter, J., Taylor, K. D., Cai, J., Eckfeldt, J., ... Franceschini, N. (2017). African ancestry-specific alleles and kidney disease risk in hispanics/latinos. Journal of the American Society of Nephrology, 28(3), 915-922. https://doi.org/10.1681/ASN.2016030357