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Morio Ueno, Masakazu Nakano, Hiroko Nakagawa, Hiroko Adachi, Yuichi Tokuda, Yoko Ikeda, Chie Sotozono, Kei Tashiro, Shigeru Kinoshita; Genome-wide association study of Fuchs endothelial corneal dystrophy in a Japanese population. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5657.
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Fuchs endothelial corneal dystrophy (FECD, MIM: 136800) is an inherited, progressive degenerative disease that affects the corneal endothelium. In the United States, FECD is regarded as a common disease, i.e., ~5% of the population over 40 years of age suffer from the disease, whereas the prevalence of FECD is less amongst the Japanese population. A genome-wide association study (GWAS) revealed that an intronic variant (rs613872) in transcription factor 4 (TCF4) is a significant risk factor of late-onset FECD in Caucasians, and the expansion of the cystosine-thymine-guanine (CTG) trinucleotide repeat in the third intron of TCF4 was found to be associated with FECD in those patients. We also found that the CTG repeat in TCF4 was significantly expanded in Japanese FECD patients compared to the controls, although the frequency of patients possessing expanded repeats was less than that in Caucasian patients. These results suggested that additional undiscovered variants are likely involved in the pathogenesis of FECD in Japanese.
In this study, we performed a GWAS to identify novel susceptible variants in Japanese FECD patients. This study involved 55 Japanese FECD patients (17 males and 38 females, mean age: 68.7 years) and 445 Japanese controls (150 males and 295 females, mean age: 67.3 years). Genomic DNA from the subjects was genotyped on an Infinium HumanCoreExome BeadChip (illumina®, Inc.) with 538,448 variants according to the manufacturer’s protocol. After removing samples and variants that failed to pass the quality control testing, the genotype data were applied to a GWAS analyzing 278,032 autosomal variants.
We were unable to obtain any significant variants within 1 Mb of the TCF4 locus. Especially, rs613872 in TCF4 turned out to be monomorphic in our population, which was supported by the Japanese data based on NCBI dbSNP. By contrast, we succeeded in obtaining some suggestive loci other than the TCF4 locus, which seemed to be associated with Japanese FECD patients. In particular, a genome-wide significant variant (P < 5.0 x 10-8) was identified at 6q15.
Our results suggest the existence of novel FECD-associated variants in a Japanese population, and should provide a foundation for future studies to reveal the mechanism determining the FECD pathogenesis in different populations.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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