{"doi":"10.1167/iovs.61.2.48","title":"Association of a Variant in VWA3A with Response to Anti-Vascular Endothelial Growth Factor Treatment in Neovascular AMD","abstract":"Purpose: Anti-vascular endothelial growth factor (VEGF) therapy for neovascular AMD (nvAMD) obtains a variable outcome. We performed a genome-wide association study for anti-VEGF treatment response in nvAMD to identify variants potentially underlying such a variable outcome. Methods: Israeli patients with nvAMD who underwent anti-VEGF treatment (n = 187) were genotyped on a whole exome chip containing approximately 500,000 variants. Genotyping was correlated with delta visual acuity (deltaVA) between baseline and after three injections of anti-VEGF. Top principal components, age, and baseline VA were included in the analysis. Two lead associated variants were genotyped in an independent validation set of patients with nvAMD (n = 108). Results: Linear regression analysis on 5,353,842 variants revealed five exonic variants with an association P value of less than 6 × 10-5. The top variant in the gene VWA3A (P = 1.77 × 10-6) was tested in the validation cohort. The minor allele of the VWA3A variant was associated with worse response to treatment (P = 0.02). The average deltaVA of discovery plus validation was -0.214 logMAR (≈ a gain of 10.7 Early Treatment Diabetic Retinopathy Study letters) for homozygote for the major allele, 0.172 logMAR for heterozygotes (≈ a loss of 8.6 Early Treatment Diabetic Retinopathy Study letters), and 0.21 logMAR for homozygote for the minor allele (≈ a loss of 10.5 Early Treatment Diabetic Retinopathy Study letters). Minor allele carriers had a higher frequency of macular hemorrhage at baseline. Conclusions: An VWA3A gene variant was associated with worse response to anti-VEGF treatment in Israeli patients with nvAMD. The VWA3A protein is a precursor of the multimeric von Willebrand factor which is involved in blood coagulation, a system previously associated with nvAMD.","journal":"Investigative Ophthalmology & Visual Science","year":2020,"id":83953,"datarank":0.3596842909197557,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.0,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":278859,"name":"Gala Beykin","orcid":"0000-0003-2025-545X","position":1,"is_corresponding":false},{"id":227969,"name":"Elior Rahmani","orcid":"0000-0002-9017-2070","position":2,"is_corresponding":false},{"id":431628,"name":"Regev Schweiger","orcid":"0000-0003-2450-8901","position":3,"is_corresponding":false},{"id":432936,"name":"Gal Barel","orcid":null,"position":4,"is_corresponding":false},{"id":344210,"name":"Shira Hagbi-Levi","orcid":"0000-0002-2891-0079","position":5,"is_corresponding":false},{"id":431629,"name":"Sarah Elbaz-Hayoun","orcid":"0009-0006-8605-5775","position":6,"is_corresponding":false},{"id":432937,"name":"Batya Rinsky","orcid":null,"position":7,"is_corresponding":false},{"id":432938,"name":"Michal Ganiel","orcid":null,"position":8,"is_corresponding":false},{"id":289878,"name":"Shai Carmi","orcid":"0000-0002-0188-2610","position":9,"is_corresponding":false},{"id":227975,"name":"Eran Halperin","orcid":"0000-0002-2373-3691","position":10,"is_corresponding":false},{"id":54569,"name":"Itay Chowers","orcid":"0000-0003-1897-4973","position":11,"is_corresponding":false},{"id":344209,"name":"Michelle Grunin","orcid":"0000-0002-3155-2858","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T21:54:50.827092Z","pmid":"32106291","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}