TY - JOUR
T1 - African ancestry-specific alleles and kidney disease risk in hispanics/latinos
AU - Kramer, Holly J.
AU - Stilp, Adrienne M.
AU - Laurie, Cathy C.
AU - Reiner, Alex P.
AU - Lash, James
AU - Daviglus, Martha L.
AU - Rosas, Sylvia E.
AU - Ricardo, Ana C.
AU - Tayo, Bamidele O.
AU - Flessner, Michael F.
AU - Kerr, Kathleen F.
AU - Peralta, Carmen
AU - Durazo-Arvizu, Ramon
AU - Conomos, Matt
AU - Thornton, Timothy
AU - Rotter, Jerome
AU - Taylor, Kent D.
AU - Cai, Jainwen
AU - Eckfeldt, John
AU - Chen, Han
AU - Papanicolau, George
AU - Franceschini, Nora
N1 - Publisher Copyright:
© 2017 by the American Society of Nephrology.
PY - 2017/3
Y1 - 2017/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85021851183&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85021851183&partnerID=8YFLogxK
U2 - 10.1681/ASN.2016030357
DO - 10.1681/ASN.2016030357
M3 - Article
C2 - 27650483
AN - SCOPUS:85021851183
SN - 1046-6673
VL - 28
SP - 915
EP - 922
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 3
ER -