Heritability of measures of kidney disease among Zuni Indians: the Zuni Kidney Project.
BACKGROUND
The long-term goal of the GKDZI (Genetics of Kidney Disease in Zuni Indians) Study is to identify genes, environmental factors, and genetic-environmental interactions that modulate susceptibility to renal disease and intermediate phenotypes.


METHODS
A community-based participatory research approach was used to recruit family members of individuals with kidney disease.


METHODS
The study was conducted in the Zuni Indians, a small endogamous tribe located in rural New Mexico. We recruited members of extended families, ascertained through a proband with kidney disease and at least 1 sibling with kidney disease. 821 participants were recruited, comprising 7,702 relative pairs. PREDICTOR OUTCOMES & MEASUREMENTS: Urine albumin-creatinine ratio (UACR) and hematuria were determined in 3 urine samples and expressed as a true ratio. Glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) Study equation modified for American Indians. Probands were considered to have kidney disease if UACR was >or=0.2 in 2 or more of 3 spot urine samples or estimated GFR was decreased according to the CRIC (Chronic Renal Insufficiency Cohort) Study criteria.


RESULTS
Kidney disease was identified in 192 participants (23.4%). There were significant heritabilities for estimated GFR, UACR, serum creatinine, serum urea nitrogen, and uric acid and a variety of phenotypes related to obesity, diabetes, and cardiovascular disease. There were significant genetic correlations of some kidney-related phenotypes with these other phenotypes.


CONCLUSIONS
Limitations include absence of renal biopsy, possible misclassification bias, lack of direct GFR measurements, and failure to include all possible environmental interactions.


CONCLUSIONS
Many phenotypes related to kidney disease showed significant heritabilities in Zuni Indians, and there were significant genetic correlations with phenotypes related to obesity, diabetes, and cardiovascular disease. The study design serves as a paradigm for the conduct of research in relatively isolated, endogamous, underserved populations.
MacCluer
Jean W
JW
Southwest Foundation for Biomedical Research, San Antonio, TX, USA.
Scavini
Marina
M
Shah
Vallabh O
VO
Cole
Shelley A
SA
Laston
Sandra L
SL
Voruganti
V Saroja
VS
Paine
Susan S
SS
Eaton
Alfred J
AJ
Comuzzie
Anthony G
AG
Tentori
Francesca
F
Pathak
Dorothy R
DR
Bobelu
Arlene
A
Bobelu
Jeanette
J
Ghahate
Donica
D
Waikaniwa
Mildred
M
Zager
Philip G
PG
D000418:Albumins / Q000378:metabolism; D001806:Blood Urea Nitrogen; D055812:Community-Based Participatory Research; D003404:Creatinine / Q000652:urine; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D005919:Glomerular Filtration Rate; D006417:Hematuria / Q000208:ethnology; D006801:Humans; D007198:Indians, North American; D009516:New Mexico; D009765:Obesity / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D051436:Renal Insufficiency, Chronic / Q000208:ethnology* / Q000235:genetics*
D000418:Albumins; D003404:Creatinine