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PLoS One. 2013 Dec 17;8(12):e81888. doi: 10.1371/journal.pone.0081888. eCollection 2013.

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).

Author information

  • 1Department of Medicine, The University of Texas Health Science Center, San Antonio, Texas, United States of America.
  • 2Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America.
  • 3Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
  • 4Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, United States of America.
  • 5Department of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
  • 6Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
  • 7Department of Medicine, University of California, Los Angeles, California, United States of America.
  • 8Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, United States of America.
  • 9Department of Pediatrics, Harbor-University of California Los Angeles Medical Center, Torrance, California, United States of America.
  • 10Department of Medicine, Harbor-University of California Los Angeles Medical Center, Torrance, California, United States of America.
  • 11National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
  • 12Department of Epidemiology and Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
  • 13University of New Mexico, Albuquerque, New Mexico, United States of America.
  • 14National Human Genome Research Institute, NIH, Bethesda, Maryland, United States of America.
  • 15Center for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
  • 16Department of Medicine, University of California, Irvine, California, United States of America.
  • 17Department of Epidemiology and Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America ; Department of Pediatrics, University of Toronto, Toronto, Canada.

Abstract

OBJECTIVE:

Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR.

METHODS:

Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula.

RESULTS:

The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome.

CONCLUSION:

The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

PMID:
24358131
[PubMed - indexed for MEDLINE]
PMCID:
PMC3866106
Free PMC Article
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