Abstract
Purpose: :
Genome-wide association studies (GWAS) had identified major genes for age-related macular degeneration (AMD). However, no GWAS for polypoidal choroidal vasculopahty (PCV) has been reported. This study is to identify the susceptibility loci for PCV using GWAS.
Methods: :
The first phase of our study included 106 PCV patients and 754 non-PCV controls. All study subjects are Han Chinese recruited in Hong Kong after complete ophthalmic investigations including indocyanine green angiography. The Illumina HumanHapCNV370 beadchip was used for genotyping, followed by a pipeline of data analysis conducted with the use of both the PLINK and snpMatrix statistical packages.
Results: :
The total genotyping rate in the individuals was >99.5%. After frequency and genotyping pruning, approximately 293,000 single-nucleotide polymorphisms (SNPs) remained for association analysis. The genomic inflation factor was 1.022, indicating a very low level of population stratification. Five SNPs on chromosomes 5, 8, 9, 12 and 22, respectively, showed the strongest associations, with a P value <10-5. Another 35 SNPs had P values <10-4. A known AMD-associated SNP, CFH rs1329428, was among these top SNPs, while the remainders have not been implicated in AMD before. Replication and validation of those SNPs showing P values lower than 10-4 in several study cohorts are in progress.
Conclusions: :
Our study should lead to the identification of novel loci for PCV after completion of sample analysis of all study cohorts and the third phase of the project, including biological investigations of the associated SNPs.
Keywords: genetics • age-related macular degeneration • gene mapping