Skip to main content

Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy.

Publication ,  Journal Article
Li, Y-J; Minear, MA; Rimmler, J; Zhao, B; Balajonda, E; Hauser, MA; Allingham, RR; Eghrari, AO; Riazuddin, SA; Katsanis, N; Gottsch, JD ...
Published in: PLoS One
April 20, 2011

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

April 20, 2011

Volume

6

Issue

4

Start / End Page

e18044

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor 4
  • Polymorphism, Single Nucleotide
  • Models, Genetic
  • Introns
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Markers
  • Genetic Linkage
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Li, Y.-J., Minear, M. A., Rimmler, J., Zhao, B., Balajonda, E., Hauser, M. A., … Afshari, N. A. (2011). Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy. PLoS One, 6(4), e18044. https://doi.org/10.1371/journal.pone.0018044
Li, Yi-Ju, Mollie A. Minear, Jacqueline Rimmler, Bei Zhao, Elmer Balajonda, Michael A. Hauser, R Rand Allingham, et al. “Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy.PLoS One 6, no. 4 (April 20, 2011): e18044. https://doi.org/10.1371/journal.pone.0018044.
Li Y-J, Minear MA, Rimmler J, Zhao B, Balajonda E, Hauser MA, et al. Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy. PLoS One. 2011 Apr 20;6(4):e18044.
Li, Yi-Ju, et al. “Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy.PLoS One, vol. 6, no. 4, Apr. 2011, p. e18044. Pubmed, doi:10.1371/journal.pone.0018044.
Li Y-J, Minear MA, Rimmler J, Zhao B, Balajonda E, Hauser MA, Allingham RR, Eghrari AO, Riazuddin SA, Katsanis N, Gottsch JD, Gregory SG, Klintworth GK, Afshari NA. Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy. PLoS One. 2011 Apr 20;6(4):e18044.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

April 20, 2011

Volume

6

Issue

4

Start / End Page

e18044

Location

United States

Related Subject Headings

  • Transcription Factors
  • Transcription Factor 4
  • Polymorphism, Single Nucleotide
  • Models, Genetic
  • Introns
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Markers
  • Genetic Linkage