PubMed ID: 22045388
Author(s): Louttit MD, Kopplin LJ, Igo RP Jr, Fondran JR, Tagliaferri A, Bardenstein D, Aldave AJ, Croasdale CR, Price MO, Rosenwasser GO, Lass JH, Iyengar SK; FECD Genetics Multi-Center Study Group. A multicenter study to map genes for Fuchs endothelial corneal dystrophy: baseline characteristics and heritability. Cornea. 2012 Jan;31(1):26-35. doi: 10.1097/ICO.0b013e31821c9b8f. PMID 22045388
Journal: Cornea, Volume 31, Issue 1, Jan 2012
PURPOSE 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.