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 journalArticlepeer-review

28 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

Bibliographical note

Funding Information:
The baseline examination of HCHS/SOL was carried out as a collaborative study supported by contracts from the National Heart, Lung, and Blood Institute (NHLBI) to the University of North Carolina (N01-HC65233), University of Miami (N01-HC65234), Albert Einstein College of Medicine (N01-HC65235), Northwestern University (N01-HC65236), and San Diego State University (N01-HC65237). The following Institutes/Centers/Offices contributed to the first phase of HCHS/SOL through a transfer of funds to the NHLBI: National Institute on Minority Health and Health Disparities, National Institute on Deafness and Other Communication Disorders, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Neurological Disorders and Stroke, National Institutes of Health Institution–Office of Dietary Supplements. The Genetic Analysis Center at Washington University was supported by NHLBI and NIDCR contracts (HHSN268201300005C AM03 and MOD03). Additional analysis support was provided by the NHLBI grant HL123677-01 (N.F.). Genotyping efforts were supported by NHLBI HSN 26220/20054C, National Center for Advancing Translational Sciences Clinical and Translational Science Institute grant UL1TR000124, and NIDDK Diabetes Research Center grant DK063491.

Publisher Copyright:
© 2017 by the American Society of Nephrology.

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