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

Moeen Riaz, Laura Lores-Motta, Andrea Richardson, Yi Lu, Grant Montgomery, Amer Omar, Robert Koenekoop, John Chen, Philipp Muether, Lebriz Altay, Tina Schick, Sascha Fauser, Dzenita Smailhodzic, Freekje van Ason, Eiko de Jong, Carel Hoyng, Kathryn Burdon, Stuart Macgregor, Robyn Guymer, Anneke den HollanderPaul Baird

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number37924
Number of pages10
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016

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