Quantitative genetics of renal function: tackling complexities of the eGFR phenotype in gene mapping studies

American Indians have a disproportionately high rate of kidney disease likely due to a combination of increased environmental and genetic risk factors. In an attempt to localize genes influencing kidney disease risk factors, we performed a genome wide scan of estimated glomerular filtration rate on participants of the Strong Heart Family Study. Over 3 600 men and women from 13 American Indian tribes were recruited from 3 centers (Arizona, North and South Dakota, Oklahoma). Using SOLAR 2.1.2, multipoint variance component linkage analysis was performed in each center as well as the entire cohort after controlling for center effects. Two modeling strategies were utilized: model 1 incorporated age, sex and interaction terms and model 2 additionally controlled for diabetic status, systolic and diastolic blood pressure, body mass index, low density lipoproteins, high density lipoproteins, triglycerides and smoking status. Significant evidence for linkage in Arizona lay on 12p12.2 at 39cM nearest marker D12S310 (LOD=3.5). Additional loci with suggestive evidence for linkage were detected at 1p36.31 (LOD=2.0–2.3), 2q33.3 (LOD=1.8) and 9q34.2 (LOD=2.4). No significant evidence for additive interaction with diabetes, hypertension or obesity was noted. In conclusion, we found 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.