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https://doi.org/10.1371/journal.pone.0018044
Title: | Replication of tcf4 through association and linkage studies in late-onset fuchs endothelial corneal dystrophy | Authors: | Li Y.-J. Minear M.A. Rimmler J. Zhao B. Balajonda E. Hauser M.A. Allingham R.R. Eghrari A.O. Riazuddin S.A. Katsanis N. Gottsch J.D. Gregory S.G. Klintworth G.K. Afshari N.A. |
Keywords: | protein TCF4 T cell factor protein unclassified drug basic helix loop helix leucine zipper transcription factor TCF4 protein, human transcription factor adult allele article chromosome 18 congenital cornea dystrophy controlled study dominant gene family history female gene frequency gene function gene location gene replication gene targeting genetic association genetic linkage genetic model genetic predisposition genetic variability genotype heterozygote human male marker gene onset age pathogenesis recessive gene scoring system single nucleotide polymorphism validation process biological model congenital cornea dystrophy genetic association genetic marker genetics intron Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Chromosomes, Human, Pair 18 Fuchs' Endothelial Dystrophy Genetic Linkage Genetic Markers Genetic Predisposition to Disease Genome-Wide Association Study Humans Introns Models, Genetic Polymorphism, Single Nucleotide Transcription Factors |
Issue Date: | 2011 | Citation: | Li Y.-J., Minear M.A., Rimmler J., Zhao B., Balajonda E., Hauser M.A., Allingham R.R., Eghrari A.O., Riazuddin S.A., Katsanis N., Gottsch J.D., Gregory S.G., Klintworth G.K., Afshari N.A. (2011). Replication of tcf4 through association and linkage studies in late-onset fuchs endothelial corneal dystrophy. PLoS ONE 6 (4) : e18044. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0018044 | Rights: | Attribution 4.0 International | Abstract: | Fuchs endothelial corneal dystrophy (FECD) is a common, late-onset disorder of the corneal endothelium. Although progress has been made in understanding the genetic basis of FECD by studying large families in which the phenotype is transmitted in an autosomal dominant fashion, a recently reported genome-wide association study identified common alleles at a locus on chromosome 18 near TCF4 which confer susceptibility to FECD. Here, we report the findings of our independent validation study for TCF4 using the largest FECD dataset to date (450 FECD cases and 340 normal controls). Logistic regression with sex as a covariate was performed for three genetic models: dominant (DOM), additive (ADD), and recessive (REC). We found significant association with rs613872, the target marker reported by Baratz et al.(2010), for all three genetic models (DOM: P = 9.33×10-35; ADD: P = 7.48×10-30; REC: P = 5.27×10-6). To strengthen the association study, we also conducted a genome-wide linkage scan on 64 multiplex families, composed primarily of affected sibling pairs (ASPs), using both parametric and non-parametric two-point and multipoint analyses. The most significant linkage region localizes to chromosome 18 from 69.94cM to 85.29cM, with a peak multipoint HLOD = 2.5 at rs1145315 (75.58cM) under the DOM model, mapping 1.5 Mb proximal to rs613872. In summary, our study presents evidence to support the role of the intronic TCF4 single nucleotide polymorphism rs613872 in late-onset FECD through both association and linkage studies. © 2011 Li et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/162053 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0018044 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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