Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United States.
Citation | Brown, Lisa A, et al. “Admixture Mapping Identifies an Amerindian Ancestry Locus Associated With Albuminuria in Hispanics in the United States”. 2017. Journal of the American Society of Nephrology : JASN, vol. 28, no. 7, 2017, pp. 2211–2220. |
Center | UCSD-UCLA |
Author | Lisa A Brown, Tamar Sofer, Adrienne M Stilp, Leslie J Baier, Holly J Kramer, Ivica Masindova, Daniel Levy, Robert L Hanson, Ashley E Moncrieft, Susan Redline, Sylvia E Rosas, James P Lash, Jianwen Cai, Cathy C Laurie, Sharon Browning, Timothy Thornton, Nora Franceschini |
Keywords | albumins, albuminuria, ethnic groups, ethnic minority, genomics, human genetics |
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. |
Year of Publication |
2017
|
Journal |
Journal of the American Society of Nephrology : JASN
|
Volume |
28
|
Issue |
7
|
Number of Pages |
2211-2220
|
Date Published |
07/2017
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ISSN Number |
1533-3450
|
DOI |
10.1681/ASN.2016091010
|
Alternate Journal |
J. Am. Soc. Nephrol.
|
PMID |
28137830
|
PMCID |
PMC5491288
|
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