title: Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the 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 (P<5.7 × 10-5). Within this locus, two common variants located at the proapoptoticBCL2L11gene 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.
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Brown
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Tamar
authors.initials: T
authors.lastname: Sofer
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Stilp
authors.affiliation: Epidemiology and Clinical Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Baier
authors.affiliation: Department of Public Health Sciences and Medicine, Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, Illinois.
authors.forename: Holly J
authors.initials: HJ
authors.lastname: Kramer
authors.affiliation: Epidemiology and Clinical Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona.
authors.forename: Ivica
authors.initials: I
authors.lastname: Masindova
authors.affiliation: The Framingham Heart Study, Framingham, Massachusetts, and Population Sciences Branch, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: Epidemiology and Clinical Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.affiliation: Department of Psychology, University of Miami, Miami, Florida.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Moncrieft
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: Department of Medicine, Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Rosas
authors.affiliation: Department of Medicine, Division of Nephrology and Institute for Minority Health Research, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: James P
authors.initials: JP
authors.lastname: Lash
authors.affiliation: Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; and.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Sharon
authors.initials: S
authors.lastname: Browning
authors.affiliation: Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Timothy
authors.initials: T
authors.lastname: Thornton
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina noraf@unc.edu.
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
mesh_terms: D000419:Albuminuria / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D005787:Gene Frequency; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008875:Middle Aged; D044469:Racial Groups / Q000235:genetics*; D014481:United States; D044465:White People; D001741:Black or African American
keywords: albumins; albuminuria; ethnic groups; ethnic minority; genomics; human genetics