title: A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, The University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Farook
authors.initials: F
authors.lastname: Thameem
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Igo
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Carl
authors.initials: C
authors.lastname: Langefeld
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Schelling
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
authors.forename: Ravindranath
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: Department of Medicine, University of California, Los Angeles, California, United States of America.
authors.forename: Susanne B
authors.initials: SB
authors.lastname: Nicholas
authors.affiliation: Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, United States of America.
authors.forename: Katrina A B
authors.initials: KA
authors.lastname: Goddard
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.affiliation: Department of Pediatrics, Harbor-University of California Los Angeles Medical Center, Torrance, California, United States of America.
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Medicine, Harbor-University of California Los Angeles Medical Center, Torrance, California, United States of America.
authors.forename: Eli
authors.initials: E
authors.lastname: Ipp
authors.affiliation: National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.affiliation: Department of Epidemiology and Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Meoni
authors.affiliation: University of New Mexico, Albuquerque, New Mexico, United States of America.
authors.forename: Vallabh O
authors.initials: VO
authors.lastname: Shah
authors.affiliation: National Human Genome Research Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Smith
authors.affiliation: Center for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.affiliation: University of New Mexico, Albuquerque, New Mexico, United States of America.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Zager
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, United States of America.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.affiliation: Department of Medicine, University of California, Irvine, California, United States of America.
authors.forename: Madeline V
authors.initials: MV
authors.lastname: Pahl
authors.affiliation: Department of Epidemiology and Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America ; Department of Pediatrics, University of Toronto, Toronto, Canada.
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.affiliation: Department of Epidemiology and Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.affiliation: National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rebekah S
authors.initials: RS
authors.lastname: Rasooly
authors.affiliation: Department of Medicine, Harbor-University of California Los Angeles Medical Center, Torrance, California, United States of America.
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Adler
authors.affiliation: Department of Medicine, The University of Texas Health Science Center, San Antonio, Texas, United States of America.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Abboud
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: John R
authors.initials: JR
authors.lastname: Sedor
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D044465:White People / Q000235:genetics