Research Summary: Replication of TCF4 through Association and Linkage Studies in Late-Onset Fuchs Endothelial Corneal Dystrophy

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 = 9.33×10−35P = 7.48×10−30P = 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.

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Publisher: Public Library of Science

Date Published: 20-April-2011

Author(s): Li Y., Minear M., Rimmler J., Zhao B., Balajonda E., Hauser M., Allingham R., Eghrari A., Riazuddin S., Katsanis N., Gottsch J., Gregory S., Klintworth G., Afshari N.

Link: https://doi.org/10.1371/journal.pone.0018044

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