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

TitleAfrican Ancestry-Specific Alleles and Kidney Disease Risk in Hispanics/Latinos.
Publication TypePublication
Year2017
AuthorsKramer HJ, Stilp AM, Laurie CC, Reiner AP, Lash J, Daviglus ML, Rosas SE, Ricardo AC, Tayo BO, Flessner MF, Kerr KF, Peralta C, Durazo-Arvizu R, Conomos M, Thornton T, Rotter J, Taylor KD, Cai J, Eckfeldt J, Chen H, Papanicolau G, Franceschini N
JournalJ Am Soc Nephrol
Volume28
Issue3
Pagination915-922
Date Published2017 Mar
ISSN1533-3450
KeywordsAfrican Continental Ancestry Group, Alleles, Female, genome-wide association study, Hispanic Americans, Humans, Male, Middle Aged, Renal Insufficiency, Chronic, Risk Factors
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 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit gene [] 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 alleles (1.0% versus 0.1%) and the variant (2.0% versus 0.7%). In the Caribbean background group, presence of alleles (2 versus 0/1 copies) or the 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 (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 variant among all participants, with the strongest association in the Caribbean background group (=3.1×10 versus =9.3×10 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.

DOI10.1681/ASN.2016030357
Alternate JournalJ Am Soc Nephrol
PubMed ID27650483
PubMed Central IDPMC5328161
Grant ListHHSN268201300005C / HL / NHLBI NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
R21 HL123677 / HL / NHLBI NIH HHS / United States
K23 DK094829 / DK / NIDDK NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
MS#: 
0335
Manuscript Lead/Corresponding Author Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
ECI: 
Yes
Manuscript Affiliation: 
Coordinating Center - Collaborative Studies Coordinating Center - UNC at Chapel Hill
Manuscript Status: 
Published