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GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration

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posted on 2023-05-18, 23:56 authored by Riaz, M, Lores-Motta, L, Richardson, AJ, Lu, Y, Montgomery, G, Omar, A, Koenekoop, RK, Chen, J, Muether, P, Altay, L, Schick, T, Fauser, S, Smailhodzic, D, van Asten, F, de Jong, EK, Hoyng, CB, Kathryn BurdonKathryn Burdon, MacGregor, S, Guymer, RH, den Hollander, AI, Baird, PN
Pooled DNA based GWAS to determine genetic association of SNPs with visual acuity (VA) outcome in anti-vascular endothelial growth factor (anti-VEGF) treated neovascular age-related macular degeneration (nAMD) patients. We performed pooled DNA based GWAS on 285 anti-VEGF treated nAMD patients using high density Illumina 4.3 M array. Primary outcome was change in VA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 6 months of anti-VEGF treatment (patients who lost ≥5 ETDRS letters classified as non-responders and all remaining classified as responders). GWAS analysis identified 44 SNPs of interest: 37 with strong evidence of association (p < 9 × 10-8), 2 in drug resistance genes (p < 5 × 10-6) and 5 nonsynonymous changes (p < 1 × 10-4). In the validation phase, individual genotyping of 44 variants showed three SNPs (rs4910623 p = 5.6 × 10-5, rs323085 p = 6.5 × 10-4 and rs10198937 p = 1.30 × 10-3) remained associated with VA response at 6 months. SNP rs4910623 also associated with treatment response at 3 months (p = 1.5 × 10-3). Replication of these three SNPs in 376 patients revealed association of rs4910623 with poor VA response after 3 and 6 months of treatment (p = 2.4 × 10-3 and p = 3.5 × 10-2, respectively). Meta-analysis of both cohorts (673 samples) confirmed association of rs4910623 with poor VA response after 3 months (p = 1.2 × 10-5) and 6 months (p = 9.3 × 10-6) of treatment in nAMD patients.


Publication title

Scientific Reports



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Menzies Institute for Medical Research


Nature Publishing Group

Place of publication

United Kingdom

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Copyright 2016 the Author(s). Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

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  • Open

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Clinical health not elsewhere classified

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