{"doi":"10.1093/hmg/ddad189","title":"Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration","abstract":"Genome-wide association studies have contributed extensively to the discovery of disease-associated common variants. However, the genetic contribution to complex traits is still largely difficult to interpret. We report a genome-wide association study of 2394 cases and 2393 controls for age-related macular degeneration (AMD) via whole-genome sequencing, with 46.9 million genetic variants. Our study reveals significant single-variant association signals at four loci and independent gene-based signals in CFH, C2, C3, and NRTN. Using data from the Exome Aggregation Consortium (ExAC) for a gene-based test, we demonstrate an enrichment of predicted rare loss-of-function variants in CFH, CFI, and an as-yet unreported gene in AMD, ORMDL2. Our method of using a large variant list without individual-level genotypes as an external reference provides a flexible and convenient approach to leverage the publicly available variant datasets to augment the search for rare variant associations, which can explain additional disease risk in AMD.","journal":"Human Molecular Genetics","year":2023,"id":348676,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.635,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":16062,"name":"Matthew Zawistowski","orcid":"0000-0002-3005-083X","position":1,"is_corresponding":false},{"id":14655,"name":"Lars G. Fritsche","orcid":"0000-0002-2110-1690","position":2,"is_corresponding":false},{"id":14650,"name":"Xiaowei Zhan","orcid":"0000-0002-6249-7193","position":3,"is_corresponding":false},{"id":265844,"name":"Jennifer L. Bragg‐Gresham","orcid":"0000-0002-9069-9489","position":4,"is_corresponding":false},{"id":54560,"name":"Kari Branham","orcid":"0000-0002-2492-254X","position":5,"is_corresponding":false},{"id":651805,"name":"Jayshree Advani","orcid":"0000-0003-1416-4922","position":6,"is_corresponding":false},{"id":54612,"name":"Mohammad Othman","orcid":"0000-0002-2175-3330","position":7,"is_corresponding":false},{"id":209711,"name":"Rinki Ratnapriya","orcid":"0000-0002-0469-4631","position":8,"is_corresponding":false},{"id":16064,"name":"Tanya M. Teslovich","orcid":null,"position":9,"is_corresponding":false},{"id":213780,"name":"Dwight Stambolian","orcid":null,"position":10,"is_corresponding":false},{"id":54567,"name":"Emily Y. Chew","orcid":"0000-0003-0999-9802","position":11,"is_corresponding":false},{"id":14736,"name":"Gonçalo R. Abecasis","orcid":"0000-0003-1509-1825","position":12,"is_corresponding":false},{"id":54657,"name":"Anand Swaroop","orcid":"0000-0002-1975-1141","position":13,"is_corresponding":false},{"id":29311,"name":"Alan Kwong","orcid":"0000-0002-0779-7126","position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:12:10.335697Z","pmid":"37934784","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":[]}