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Xiaohui Li, Yelena Bykhovskaya, Kent D Taylor, David Siscovick, Jerome I Rotter, Yaron S Rabinowitz; Copy number variation (CNV) analysis using GWAS data identifies new loci associated with keratoconus. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2996.
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© ARVO (1962-2015); The Authors (2016-present)
Common or rare copy number variations (CNVs) have been found to be associated with susceptibility to a number of disorders. So far there is little evidence of relationship between CNVs and keratoconus susceptibilities.
Using genome-wide association data, we analyzed the distribution of copy number variations between 222 keratoconus cases and 947 normal controls from Cardiovascular Health Study (CHS). Genotyping was performed using Illumina 370K SNP array. Autosomal CNVs were obtained by PennCNV calling (>5 SNPs and length>50KB). A total of 3851 CNVs from 890 individuals were obtained after quality control. Association tests were performed by PLINK v1.07.
521 CNVs were identified in 98 keratoconus patients: 50.5% of these were single deletions. However, no difference of CNV rates and proportions were observed between cases and controls. 2229 genomic regions were tested for association. Using the permutation test, two duplication regions (the SATB1 gene locus at 3p24 and the ARPP-21 gene locus at 3p22) were potentially associated with keratoconus (CNVs: 15 in cases vs 0 in controls, p=5.0×10-6; and 10 in cases vs 2 in controls, p=1.0×10-5, respectively). The most significant association of a CNV deletion region with keratoconus (CNVs: 7 in cases vs 1 in controls) was identified at the RFWD2 gene at 1q25 with a p value of 5.1×10-4. Both the ARPP-21 gene and the RFWD2 gene might be involved in eye related expression, which should be investigated further. We did not identify any significant CNVs close to previously published keratoconus candidate genes.
This preliminary CNV analysis suggests that CNVs might contribute to genetic susceptibilities of kerotoconus. Given the modest sample size, validating our findings using additional data is necessary.
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