Linkage analysis of glomerular filtration rate in American Indians.
American Indians have a disproportionately high rate of kidney disease likely due to a combination of environmental and genetic factors. We performed a genome wide scan of estimated glomerular filtration rate in 3665 participants of the Strong Heart Family Study to localize genes influencing kidney disease risk factors. The participants were men and women from 13 American Indian tribes recruited from 3 centers located in Arizona, the Dakotas and Oklahoma. Multipoint variance component linkage analysis was performed for each center and on the entire cohort after controlling for center effects. Modeling strategies that incorporated age, gender and interaction terms (model 1) and another that also controlled for diabetes mellitus, systolic and diastolic blood pressure, body mass index, low density and high density lipoproteins, triglycerides and smoking status (model 2) were used. Significant evidence for linkage in the Arizona group was found on chromosome 12p12.2 at 39cM (nearest marker D12S310) using model 1. Additional loci with very suggestive evidence for linkage were detected at 1p36.31 for all groups using both models and at 2q33.3 and 9q34.2 for the Dakotas group each using model 1. No significant evidence for additive interaction with diabetes, hypertension or obesity was noted. This evidence for linkage of a quantitative trait locus influencing estimated glomerular filtration rate to a region of chromosome 12p in a large cohort of American Indians will be worth studying in more detail in the future.
UNC Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7155, USA. amy_mottl@med.unc.edu
Amy K
AK
Mottl
Suma
S
Vupputuri
Shelley A
SA
Cole
Laura
L
Almasy
Harald H H
HH
Göring
Vincent P
VP
Diego
Sandra
S
Laston
Nora
N
Franceschini
Nawar M
NM
Shara
Elisa T
ET
Lee
Lyle G
LG
Best
Richard R
RR
Fabsitz
Jean W
JW
MacCluer
Jason G
JG
Umans
Kari E
KE
North
D000293:Adolescent; D000328:Adult; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002881:Chromosomes, Human, Pair 12; D002889:Chromosomes, Human, Pair 2; D002899:Chromosomes, Human, Pair 9; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable; D012307:Risk Factors; D055815:Young Adult