African Ancestry–Specific Alleles and Kidney Disease Risk in Hispanics/Latinos

• Published in: Journal of the American Society of Nephrology Vol. 28; no. 3; pp. 915 - 922
• Main Authors: Kramer, Holly J., Stilp, Adrienne M., Laurie, Cathy C., Reiner, Alex P., Lash, James, Daviglus, Martha L., Rosas, Sylvia E., Ricardo, Ana C., Tayo, Bamidele O., Flessner, Michael F., Kerr, Kathleen F., Peralta, Carmen, Durazo-Arvizu, Ramon, Conomos, Matt, Thornton, Timothy, Rotter, Jerome, Taylor, Kent D., Cai, Jainwen, Eckfeldt, John, Chen, Han, Papanicolau, George, Franceschini, Nora
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.03.2017
• Subjects: Alleles; Black People - genetics; Clinical Epidemiology; Female; Genome-Wide Association Study; Hispanic or Latino - genetics; Humans; Male; Middle Aged; Renal Insufficiency, Chronic - epidemiology; Renal Insufficiency, Chronic - genetics; Risk Factors; genetic variants; African ancestry; albuminuria; chronic kidney disease; Hispanic; Latino
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2016030357

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 β 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 eGFR<60 ml/min per 1.73 m 2 (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 =3.1×10 −10 versus P =9.3×10 −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.