Accessibility issues or difficulties with this website?
Call 919-962-2073 or email hchsadministration@unc.edu.

Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United States.

TitleAdmixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United States.
Publication TypePublication
Year2017
AuthorsBrown LA, Sofer T, Stilp AM, Baier LJ, Kramer HJ, Masindova I, Levy D, Hanson RL, Moncrieft AE, Redline S, Rosas SE, Lash JP, Cai J, Laurie CC, Browning S, Thornton T, Franceschini N
JournalJ Am Soc Nephrol
Volume28
Issue7
Pagination2211-2220
Date Published2017 Jul
ISSN1533-3450
KeywordsAfrican Continental Ancestry Group, albuminuria, Chromosome Mapping, Continental Population Groups, European Continental Ancestry Group, Female, Gene Frequency, Hispanic Americans, Humans, Indians, North American, Male, Middle Aged, United States
Abstract

Increased urine albumin excretion is highly prevalent in Hispanics/Latinos. Previous studies have found an association between urine albumin excretion and Amerindian ancestry in Hispanic/Latino populations. Admixture between racial/ethnic groups creates long-range linkage disequilibrium between variants with different allelic frequencies in the founding populations and it can be used to localize genes. Hispanic/Latino genomes are an admixture of European, African, and Amerindian ancestries. We leveraged this admixture to identify associations between urine albumin excretion (urine albumin-to-creatinine ratio [UACR]) and genomic regions harboring variants with highly differentiated allele frequencies among the ancestral populations. Admixture mapping analysis of 12,212 Hispanic Community Health Study/Study of Latinos participants, using a linear mixed model, identified three novel genome-wide significant signals on chromosomes 2, 11, and 16. The admixture mapping signal identified on chromosome 2, spanning q11.2-14.1 and not previously reported for UACR, is driven by a difference between Amerindian ancestry and the other two ancestries (<5.7 × 10). Within this locus, two common variants located at the proapoptotic gene associated with UACR: rs116907128 (allele frequency =0.14; =1.5 × 10) and rs586283 (C allele frequency =0.35; =4.2 × 10). In a secondary analysis, rs116907128 accounted for most of the admixture mapping signal observed in the region. The rs116907128 variant is common among full-heritage Pima Indians (A allele frequency =0.54) but is monomorphic in the 1000 Genomes European and African populations. In a replication analysis using a sample of full-heritage Pima Indians, rs116907128 significantly associated with UACR (=0.01; =1568). Our findings provide evidence for the presence of Amerindian-specific variants influencing the variation of urine albumin excretion in Hispanics/Latinos.

DOI10.1681/ASN.2016091010
Alternate JournalJ Am Soc Nephrol
PubMed ID28137830
PubMed Central IDPMC5491288
Grant ListHHSN268201300005C / HL / NHLBI NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
R56 DK104806 / DK / NIDDK 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
UL1 TR001881 / TR / NCATS NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
MS#: 
0494
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