title: Genome-wide scan for estimated glomerular filtration rate in multi-ethnic diabetic populations: the Family Investigation of Nephropathy and Diabetes (FIND).
abstract: OBJECTIVE
  Diabetic nephropathy, the most common cause of end-stage renal disease, aggregates in families and specific ethnic groups. Deconstructing diabetic nephropathy into intermediate, quantitative phenotypes may increase feasibility of detecting susceptibility loci by genetic screens. Glomerular filtration rate (GFR), which characterizes diabetic nephropathy, was employed as a quantitative trait in a preliminary whole-genome scan.
  
  
  METHODS
  Estimated GFR (eGFR) was calculated for 882 diabetic sibpairs (mean age 57 years) of African-American (25.6% of total), American Indian (8.6%), European-American (14.2%), and Mexican-American (51.6%) descent enrolled in the initial phase of the Family Investigation of Nephropathy and Diabetes (FIND). A whole-genome scan was performed using 404 microsatellite markers (average spacing 9 cM) and model-free linkage analysis.
  
  
  RESULTS
  For all ethnicities combined, strong evidence for linkage was observed on chromosomes 1q43 (P = 3.6 x 10(-3)), 7q36.1 (P = 2.1 x 10(-4)), 8q13.3 (P = 4.6 x 10(-4)), and 18q23.3 (P = 2.7 x 10(-3)). Mexican-American families, who comprised the major ethnic subpopulation in FIND, contributed to linkage on chromosomes 1q43, 2p13.3, 7q36.1, 8q13.3, and 18q23.3, whereas African-American and American-Indian families displayed linkage peaks on chromosomes 11p15.1 and 15q22.3, respectively.
  
  
  CONCLUSIONS
  We have demonstrated multiple chromosomal regions linked to eGFR in a multi-ethnic collection of families ascertained by a proband with diabetic nephropathy. Identification of genetic variants within these loci that are responsible for the linkage signals could lead to predictive tests or novel therapies for subsets of patients at risk for diabetic nephropathy.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Wolstein Research Building, Rm. 1300, 10900 Euclid Ave., Cleveland, OH 44106-7281, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Schelling
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Abboud
authors.forename: Susanne B
authors.initials: SB
authors.lastname: Nicholas
authors.forename: Madeleine V
authors.initials: MV
authors.lastname: Pahl
authors.forename: John R
authors.initials: JR
authors.lastname: Sedor
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Adler
authors.forename: Nedal H
authors.initials: NH
authors.lastname: Arar
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Katrina A B
authors.initials: KA
authors.lastname: Goddard
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.forename: Eli
authors.initials: E
authors.lastname: Ipp
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.forename: Gyungah
authors.initials: G
authors.lastname: Jun
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Balakuntalam S
authors.initials: BS
authors.lastname: Kasinath
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kimmel
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Klag
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nelson
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.forename: Shannon R
authors.initials: SR
authors.lastname: Quade
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Mohammed F
authors.initials: MF
authors.lastname: Saad
authors.forename: Marina
authors.initials: M
authors.lastname: Scavini
authors.forename: Michael W
authors.initials: MW
authors.lastname: Smith
authors.forename: Kent
authors.initials: K
authors.lastname: Taylor
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Winkler
authors.forename: Philip G
authors.initials: PG
authors.lastname: Zager
authors.forename: Vallabh O
authors.initials: VO
authors.lastname: Shah
mesh_terms: D044383:Black People / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D035781:Siblings; D044465:White People / Q000235:genetics; D001741:Black or African American