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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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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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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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Journal Article
GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 45/43
/ Acuity
/ Age
/ Aged
/ Angiogenesis Inhibitors - pharmacology
/ Angiogenesis Inhibitors - therapeutic use
/ DNA
/ Female
/ Genome-Wide Association Study
/ Humanities and Social Sciences
/ Humans
/ Macular Degeneration - drug therapy
/ Macular Degeneration - genetics
/ Male
/ Polymorphism, Single Nucleotide
/ Ranibizumab - therapeutic use
/ Receptors, Odorant - genetics
/ Retinal Neovascularization - drug therapy
/ Retinal Neovascularization - genetics
/ Science
/ Single-nucleotide polymorphism
/ Vascular endothelial growth factor
/ Vascular Endothelial Growth Factor A - antagonists & inhibitors
