Authors: | 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.; Chen, H; Papanicolau, G.; Franceschini, N |
Article Title: | African Ancestry-Specific Alleles and Kidney Disease Risk in Hispanics/Latinos |
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 beta gene [HBB] variant) on the basis of imputation in 12,226 adult Hispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-to-creatinine ratios. Overall, 41.4% of participants were male, 44.6% of participants had a Caribbean 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 eGFR60 ml/min per 1.73 m2 (OR, 2.9; 95% CI, 1.5 to 5.4; and OR, 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=3.1x10-10 versus P=9.3x10-3 for the Mainland background group). In conclusion, African-specific alleles associate with CKD in Hispanics/Latinos, but allele frequency varies by Hispanic/Latino background/ancestry. |
Journal Title: | Journal of the American Society of Nephrology : JASN |
ISSN: | 1533-3450; 1046-6673 |
Publisher: | by the American Society of Nephrology |
Journal Place: | United States |
Date Published: | 2016 |
Language: | ENG |
DOI/URL: |
ASN.2016030357 |
Notes: | LR: 20160921; CI: Copyright (c) 2016; JID: 9013836; OTO: NOTNLM; 2016/03/26 [received]; 2016/07/26 [accepted]; aheadofprint |