Citation: Clinical Journal of The American Society of Nephrology: CJASN. 9(1):150-8, 2014 Jan..Journal: Clinical journal of the American Society of Nephrology : CJASN.ISSN: 1555-9041.Full author list: Franceschini N; Haack K; Almasy L; Laston S; Lee ET; Best LG; Fabsitz RR; MacCluer JW; Howard BV; Umans JG; Cole SA.UI/PMID: 24311711.Subject(s): Adult | Age Factors | Albuminuria/eh [Ethnology] | Albuminuria/ge [Genetics] | Female | Gene Frequency | *Genetic Loci | Genetic Predisposition to Disease | Glomerular Filtration Rate/ge [Genetics] | Haplotypes | Heredity | Humans | *Indians, North American/ge [Genetics] | Kidney/pp [Physiopathology] | Kidney Diseases/eh [Ethnology] | *Kidney Diseases/ge [Genetics] | Kidney Diseases/pp [Physiopathology] | Male | Middle Aged | Pedigree | Phenotype | Polymorphism, Single Nucleotide | Risk Factors | Sex Factors | United States/ep [Epidemiology] | Young AdultInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal Article | Multicenter Study | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov'tDigital Object Identifier: http://dx.doi.org/10.2215/CJN.02300213 (Click here)Abbreviated citation: Clin J Am Soc Nephrol. 9(1):150-8, 2014 Jan.Abstract: BACKGROUND AND OBJECTIVES: CKD disproportionally affects American Indians, who similar to other populations, show genetic susceptibility to kidney outcomes. Recent studies have identified several loci associated with kidney traits, but their relevance in American Indians is unknown.Abstract: DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study used data from a large, family-based genetic study of American Indians (the Strong Heart Family Study), which includes 94 multigenerational families enrolled from communities located in Oklahoma, the Dakotas, and Arizona. Individuals were recruited from the Strong Heart Study, a population-based study of cardiovascular disease in American Indians. This study selected 25 single nucleotide polymorphisms in 23 loci identified from recently published kidney-related genome-wide association studies in individuals of European ancestry to evaluate their associations with kidney function (estimated GFR; individuals 18 years or older, up to 3282 individuals) and albuminuria (urinary albumin to creatinine ratio; n=3552) in the Strong Heart Family Study. This study also examined the association of single nucleotide polymorphisms in the APOL1 region with estimated GFR in 1121 Strong Heart Family Study participants. GFR was estimated using the abbreviated Modification of Diet in Renal Disease Equation. Additive genetic models adjusted for age and sex were used.Abstract: RESULTS: This study identified significant associations of single nucleotide polymorphisms with estimated GFR in or nearby PRKAG2, SLC6A13, UBE2Q2, PIP5K1B, and WDR72 (P<2.1 x 10(-3) to account for multiple testing). Single nucleotide polymorphisms in these loci explained 2.2% of the estimated GFR total variance and 2.9% of its heritability. An intronic variant of BCAS3 was significantly associated with urinary albumin to creatinine ratio. APOL1 single nucleotide polymorphisms were not associated with estimated GFR in a single variant test or haplotype analyses, and the at-risk variants identified in individuals with African ancestry were not detected in DNA sequencing of American Indians.Abstract: CONCLUSION: This study extends the genetic associations of loci affecting kidney function to American Indians, a population at high risk of kidney disease, and provides additional support for a potential biologic relevance of these loci across ancestries.