Purpose: To better understand pachychoroid diseases, which are recently garnering attention, a genome-wide association study (GWAS) was conducted with an aim to discover genes related to choroidal thickness in eyes with age-related macular degeneration (AMD).
Subjects and methods: Subjects comprised 707 AMD patients whose subfoveal choroidal thickness was measured on retinal optical coherence tomography images, and blood collection was performed at the Kyoto University Hospital. GWAS was performed on 587,048 single nucleotide polymorphisms (SNPs) on these patients.
Results: While no SNPs exhibited p<5.0×10^-8, there were three SNP regions that exhibited p<1.0×10^-5, which were RPL13AP13/RPS19P4, COL22A1/KCNK9, and ARMS2/HTRA1. While a relatively low p value of 3.78×10^-5 was found for ARMS2/HTRA1 rs10490924 (A69S), no significant correlation was observed between CFH rs800292 (I62V) and VIPR2 rs3793217 (p=0.666 and p=0.412, respectively). Analysis was performed using the 348 cases for which the axial length was measured after correcting for age, sex, and axial length. Results indicated that the p was 2.91×10^-3 for rs10490924, 0.399 for rs800292, and 0.0409 for rs3793217.
Conclusions: Previous candidate genetic studies have also reported correlations between ARMS2/HTRA1 and eye choroidal thickness in AMD, and it appears that ARMS2/HTRA1 is an important gene that determines choroidal thickness in the eyes of AMD patients. When considered in light of previous reports, it is likely that CFH determines choroidal thickness prior to AMD onset, whereas ARMS2/HTRA1 affects atrophic changes in the choroid after AMD onset. The reproducibility of RPL13AP13/RPS19P4, COL22A1/KCNK9, and VIPR2 need to be confirmed.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 123: 407-412, 2019.