title: A multicenter study to map genes for Fuchs endothelial corneal dystrophy: baseline characteristics and heritability.
abstract: OBJECTIVE
  To describe the methods for family and case-control recruitment for a multicenter genetic and associated heritability analyses of Fuchs endothelial corneal dystrophy (FECD).
  
  
  METHODS
  Twenty-nine enrolling sites with 62 trained investigators and coordinators gathered individual and family information, graded the phenotype, and collected blood and/or saliva for genetic analysis on all individuals with and without FECD. The degree of FECD was assessed in a 0 to 6 semiquantitative scale using standardized clinical methods with pathological verification of FECD on at least 1 member of each family. Central corneal thickness was measured by ultrasonic pachymetry.
  
  
  RESULTS
  Three hundred twenty-two families with 330 affected sibling pairs with FECD were enrolled and included a total of 650 sibling pairs of all disease grades. Using the entire 7-step FECD grading scale or a dichotomous definition of severe disease, heritability was assessed in families via sib-sib correlations. Both binary indicators of severe disease and semiquantitative measures of disease severity were significantly heritable, with heritability estimates of 30% for severe disease, 37% to 39% for FECD score, and 47% for central corneal thickness.
  
  
  CONCLUSIONS
  Genetic risk factors have a strong role in the severity of the FECD phenotype and corneal thickness. Genotyping this cohort with high-density genetic markers followed by appropriate statistical analyses should lead to novel loci for disease susceptibility.
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors: Megan D
authors: MD
authors: Louttit
authors: Laura J
authors: LJ
authors: Kopplin
authors: Robert P
authors: RP
authors: Igo
authors: Jeremy R
authors: JR
authors: Fondran
authors: Angela
authors: A
authors: Tagliaferri
authors: David
authors: D
authors: Bardenstein
authors: Anthony J
authors: AJ
authors: Aldave
authors: Christopher R
authors: CR
authors: Croasdale
authors: Marianne O
authors: MO
authors: Price
authors: George O
authors: GO
authors: Rosenwasser
authors: Jonathan H
authors: JH
authors: Lass
authors: Sudha K
authors: SK
authors: Iyengar
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002874:Chromosome Mapping; D015331:Cohort Studies; D003315:Cornea / Q000473:pathology; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype