{"doi":"10.1101/2024.11.08.24316962","title":"Diverse ancestry GWAS for advanced age-related macular degeneration in TOPMed-imputed and Ophthalmologically-confirmed 16,108 cases and 18,038 controls","abstract":"ABSTRACT Age-related macular degeneration (AMD) is a leading cause of blindness with $344 billion dollars global costs. In 2016, the International Age-related Macular Degeneration Genomics Consortium devised genomic data on ∼50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD in European ancestry. We have now analyzed a more densely imputed version (IAMDGC 2.0) and performed cross-ancestry GWAS in 16,108 advanced AMD cases and 18,038 AMD-free controls. This identified 28 loci at P<5×10 −8 , including two additional AMD loci compared to IAMDGC 1.0 ( SERPINA1 and CPN1 ). Fine-mapping supported one ancestry-shared signal around HTRA1/ARMS2 and nine signals around CFH without African ancestry contribution. The 52-variant genetic risk score with and the 44-variant score without CFH -variants predicted advanced AMD not only in EUR, but also in AFR and ASN (AUC=0.80/0.75, 0.65/0.64, 0.80/0.79, respectively). Our results indicate that the genetic underpinning of advanced AMD is mostly shared between ancestries.","journal":"medRxiv","year":2024,"id":492339,"datarank":0.12011386074086725,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.016141783656875436,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.016141783656875436,"corpus_percentile":28.58358474510714,"corpus_rank":9233,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":344209,"name":"Michelle Grunin","orcid":"0000-0002-3155-2858","position":1,"is_corresponding":false},{"id":1117957,"name":"Janina M. Herold","orcid":"0000-0002-2208-9742","position":2,"is_corresponding":false},{"id":1338570,"name":"Benedikt Fröhlich","orcid":null,"position":3,"is_corresponding":false},{"id":30813,"name":"Merle Behr","orcid":"0000-0002-4255-5237","position":4,"is_corresponding":false},{"id":568263,"name":"Nicholas R. Wheeler","orcid":"0000-0003-2248-8919","position":5,"is_corresponding":false},{"id":261839,"name":"William S. Bush","orcid":"0000-0002-9729-6519","position":6,"is_corresponding":false},{"id":437428,"name":"Yeunjoo E. Song","orcid":"0000-0002-7452-3731","position":7,"is_corresponding":false},{"id":368599,"name":"Xiaofeng Zhu","orcid":"0000-0003-0037-411X","position":8,"is_corresponding":false},{"id":514510,"name":"Susan H. Blanton","orcid":"0000-0002-5433-3439","position":9,"is_corresponding":false},{"id":6903,"name":"Margaret A. Pericak‐Vance","orcid":"0000-0001-7283-8804","position":10,"is_corresponding":false},{"id":21992,"name":"Iris M. Heid","orcid":"0000-0002-4122-5308","position":11,"is_corresponding":false},{"id":6896,"name":"Jonathan L. Haines","orcid":"0000-0002-4351-4728","position":12,"is_corresponding":false},{"id":1239266,"name":"Mathias Gorski","orcid":"0000-0002-9103-5860","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T02:08:49.768795Z","pmid":"39606372","pmcid":"PMC11601516","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":[]}