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J Am Soc Nephrol. 2017 Jul;28(7):2211-2220. doi: 10.1681/ASN.2016091010. Epub 2017 Jan 30.

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

Author information

1
Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
2
Epidemiology and Clinical Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona.
3
Department of Public Health Sciences and Medicine, Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, Illinois.
4
The Framingham Heart Study, Framingham, Massachusetts, and Population Sciences Branch, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland.
5
Department of Psychology, University of Miami, Miami, Florida.
6
Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
7
Department of Medicine, Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
8
Department of Medicine, Division of Nephrology and Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois.
9
Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and.
10
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina noraf@unc.edu.

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 (P<5.7 × 10-5). Within this locus, two common variants located at the proapoptotic BCL2L11 gene associated with UACR: rs116907128 (allele frequency =0.14; P=1.5 × 10-7) and rs586283 (C allele frequency =0.35; P=4.2 × 10-7). 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 (P=0.01; n=1568). Our findings provide evidence for the presence of Amerindian-specific variants influencing the variation of urine albumin excretion in Hispanics/Latinos.

KEYWORDS:

albumins; albuminuria; ethnic groups; ethnic minority; genomics; human genetics

PMID:
28137830
PMCID:
PMC5491288
DOI:
10.1681/ASN.2016091010
[Indexed for MEDLINE]
Free PMC Article

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