{"doi":"10.1167/iovs.66.13.51","title":"Diverse-Ancestry GWAS of Age-Related Macular Degeneration on 16,108 Examined Cases and 18,038 Controls","abstract":"Purpose: In 2016, the International Age-related Macular Degeneration Genomics Consortium analyzed data from approximately 50,000 individuals (IAMDGC 1.0) and identified 52 variants across 34 loci associated with advanced AMD (adAMD) in individuals of European ancestry and did not include diverse ancestries, fine-mapping per ancestry, or a predictive model with/without the contributions of one lead genetic risk locus, CFH. Therefore, we analyzed full cross-ancestry IAMDGC data, utilizing the newest imputation panel, and identified genetic risk loci across and between ancestries contributing to AMD. Methods: In this IAMDGC 2.0 analysis, we included cross-ancestry data via custom exome chip imputed genome-wide via TOPMedv2, in 16,108 ophthalmologically confirmed adAMD cases and 18,038 examined AMD-free controls. We included both male and female subjects and four diverse ancestries. Data were analyzed from June 2021 to May 2024. Results: Utilizing diverse ancestry data (cases/controls = 15,616/16,723 European, 50/357 African, 207/322 Asian, and 235/636 Other), we identified 28 loci at P < 5 × 10-8, including 2 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 predicted adAMD in all ancestries (area under the curve [AUC] = 0.80/0.75, 0.65/0.64, and 0.80/0.79, respectively). Conclusions: Our results indicate that the genetic underpinning of adAMD is mostly shared between ancestries. We also identify the CFH variant as being less relevant in specific ancestries, indicating a difference in pathogenic burden between ancestries. We increased the available genomic data for AMD over 300-fold with the IAMDGC 2.0 imputation, making it a valuable resource for further AMD genetic analysis.","journal":"Investigative Ophthalmology & Visual Science","year":2025,"id":548082,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":22.178386323199504,"corpus_rank":9377,"citation_count":1,"citer_count":1,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":62.5,"fair_percentile":81.0149801284011,"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":32,"raw_metadata":null,"created_at":"2026-07-19T02:53:53.962932Z","pmid":"41159651","pmcid":"PMC12577769","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":94.4444,"fair_a":56.25,"fair_i":0.0,"fair_r":50.0,"fair_zscore":1.1103,"fair_rationale":{"fair_score":62.5,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":94.44,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Data permitted for sharing by respective IRBs have been deposited in dbGaP under accession phs001039.v1.p1.","grounded":true,"rationale":"The paper provides a dbGaP accession (phs001039.v1.p1), which is a persistent identifier scheme.","anchors":["RDA-F1-01D — FAIR Data Maturity Model: 'Data is identified by a persistent identifier' (priorit","RDA-F1-02D — FAIR Data Maturity Model: 'Data is identified by a globally unique identifier'","FsF-F1-02D — F-UJI/FAIRsFAIR: 'Data is assigned a persistent identifier'"],"scored":true,"signal":null},{"key":"f_repository_named","label":"Named repository","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Data permitted for sharing by respective IRBs have been deposited in dbGaP under accession phs001039.v1.p1.","grounded":true,"rationale":"dbGaP is a named data repository, classified as a curated archive.","anchors":["RDA-F4-01M — FAIR Data Maturity Model: metadata is offered so it can be harvested and indexed (","NIH DMS Policy Element 4 (NOT-OD-21-014) — name the repository where data will be archived","NSTC Desirable Characteristics of Data Repositories (2022) — 'Long-Term Sustainability', 'Reten"],"scored":true,"signal":null},{"key":"f_data_availability_statement","label":"Data-availability statement","kind":"llm","weight":2.0,"fraction":1.0,"verdict":"yes","evidence":"Data Availability: GWAS summary statistics are available (upon publication) on the websites of IAMDGC data holders in USA (Cleveland; http://amdgenetics.org/ ) and Germany (Regensburg; https://www.genepi-regensburg.de/gwas-summary-statistics ). 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http://amdgenetics.org/ ) and Germany (Regensburg; https://www.genepi-regensburg.de/gwas-summary-statistics ).","grounded":true,"rationale":"The paper describes an access action (websites and dbGaP) but does not explicitly label the access level with a COAR vocabulary term.","anchors":["FsF-A1-01M — F-UJI: 'Metadata contains access level and access conditions of the data'","RDA-A1-01M — metadata contains information to enable the user to get access to the data","COAR Controlled Vocabularies — Access Rights v1.0 (open / embargoed / restricted / metadata-onl"],"scored":false,"signal":null},{"key":"a_controlled_access_for_sensitive","label":"Gatekeeper for sensitive data","kind":"llm","weight":0.5,"fraction":1.0,"verdict":"yes","evidence":"Data permitted for sharing by respective IRBs have been deposited in dbGaP under accession phs001039.v1.p1.","grounded":true,"rationale":"The paper names dbGaP, a controlled-access repository, as the institutional gatekeeper for the data.","anchors":["NIH Genomic Data Sharing Policy (NOT-OD-14-124) — controlled-access via a Data Access Committee","RDA-A1.2-01D — 'Data is accessible through an access protocol that supports authentication and ","NIH DMS Policy Element 5 (NOT-OD-21-014) — Access, Distribution, or Reuse Considerations (conse"],"scored":false,"signal":null},{"key":"a_timeline_retention","label":"Availability timing & retention","kind":"llm","weight":0.5,"fraction":0.5,"verdict":"partial","evidence":"GWAS summary statistics are available (upon publication)","grounded":true,"rationale":"The paper states when the data become available (upon publication) but does not commit to how long they persist.","anchors":["NIH DMS Plan Element 4 (NOT-OD-21-014) — Data Preservation, Access, and Associated Timelines","NSTC Desirable Characteristics (2022), Organizational Infrastructure: 'Retention Policy'","RDA-A2-01M — 'Metadata is guaranteed to remain available after data is no longer available'"],"scored":false,"signal":null}]},"I":{"name":"Interoperable","score":0.0,"criteria":[{"key":"i_open_nonproprietary_format","label":"Open file format","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No file format for the released data is named anywhere in the text.","anchors":["FsF-R1.3-02D — F-UJI: 'Data is available in a file format recommended by the target research co","RDA-R1.3-02D — data is expressed in a machine-understandable community standard","RDA-I1-01D — data uses a knowledge representation expressed in a standardised format"],"scored":true,"signal":null},{"key":"i_community_standard_vocabulary","label":"Community standard / vocabulary","kind":"llm","weight":1.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No named data or metadata community standard (e.g., MIAME, MINSEQE) is applied to the data; 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[majority verdict 'no' (3/5 passes agreed)]","anchors":["RDA-I3-01M — '(meta)data include references to other (meta)data'","RDA-I3-03M — 'metadata includes qualified references to other metadata'","FsF-I3-01M — F-UJI: 'Metadata includes links between the data and its related entities'"],"scored":false,"signal":null}]},"R":{"name":"Reusable","score":50.0,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"No license or reuse terms are stated for the data; only the article is licensed under CC BY-NC-ND. [majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-R1.1-01M — 'Metadata includes information about the licence under which the data can be reu","RDA-R1.1-02M — 'Metadata refers to a standard reuse licence'","RDA-R1.1-03M — 'Metadata refers to a machine-understandable reuse licence'"],"scored":true,"signal":null},{"key":"r_provenance_methods","label":"Provenance of the data","kind":"llm","weight":1.0,"fraction":0.5,"verdict":"partial","evidence":"We phased genomic data using Eagle version 2.4 and imputed untyped variants using minimac4.","grounded":false,"rationale":"The paper names specific tools and software versions used to produce the data. 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[majority verdict 'no' (4/5 passes agreed)]","gain":16.67,"priority":"essential","scored":true},{"key":"a_data_openly_accessible","dimension":"A","label":"Access route free of preconditions","action":"Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For clinical / human-subjects data, deposit in dbGaP or the European Genome-phenome Archive (EGA).","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"GWAS summary statistics are available (upon publication) on the websites of IAMDGC data holders","why":"The access route carries a precondition (upon publication) and controlled access via dbGaP, so it is not unconditional.","gain":8.33,"priority":"essential","scored":true},{"key":"i_open_nonproprietary_format","dimension":"I","label":"Open file format","action":"Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No file format for the released data is named anywhere in the text.","gain":8.33,"priority":"important","scored":true},{"key":"f_dataset_cited","dimension":"F","label":"Dataset formally cited","action":"Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the clinical / human-subjects repository accession (e.g. from dbGaP or the European Genome-phenome Archive (EGA)) in the reference list.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Data permitted for sharing by respective IRBs have been deposited in dbGaP under accession phs001039.v1.p1.","why":"The dataset identifier appears only in the body text (data availability statement), not in the reference list.","gain":4.17,"priority":"important","scored":true},{"key":"a_access_conditions_stated","dimension":"A","label":"Access level labelled","action":"State the access level in words, using the standard vocabulary: 'These data are open access' / 'These data are controlled access'. A reader — and a harvester — should not have to infer the access level from the presence of a download link.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"GWAS summary statistics are available (upon publication) on the websites of IAMDGC data holders in USA (Cleveland; http://amdgenetics.org/ ) and Germany (Regensburg; https://www.genepi-regensburg.de/gwas-summary-statistics ).","why":"The paper describes an access action (websites and dbGaP) but does not explicitly label the access level with a COAR vocabulary term.","gain":0.0,"priority":"important","scored":false},{"key":"i_community_standard_vocabulary","dimension":"I","label":"Community standard / vocabulary","action":"Adopt and NAME your domain's data standard — the minimum-information checklist, metadata schema, or ontology your community uses (MIAME/MINSEQE, ISA-Tab, BIDS, an OBO ontology, HL7 FHIR/OMOP) — and say which one you followed. A reporting checklist standardises your paper; it does nothing for your data. In clinical / human-subjects, describe the data with OMOP CDM, CDISC SDTM or HL7 FHIR.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No named data or metadata community standard (e.g., MIAME, MINSEQE) is applied to the data; only tools and methods are mentioned.","gain":0.0,"priority":"important","scored":false},{"key":"r_provenance_methods","dimension":"R","label":"Provenance of the data","action":"Name the instruments, kits, and software — with versions — that produced the data, not just the verbs. 'Reads were aligned' is not provenance; 'aligned with STAR v2.7.9a to GRCh38' is, because someone else can rerun it.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"We phased genomic data using Eagle version 2.4 and imputed untyped variants using minimac4.","why":"The paper names specific tools and software versions used to produce the data. [downgraded to 'partial' — no verifiable quote from the paper] [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"r_documentation_codebook","dimension":"R","label":"Documentation / codebook","action":"Ship a README and a data dictionary IN the deposit — every file, every variable, its units, its allowed values, its missing-value codes. It is the cheapest single thing that makes a dataset usable by someone who was not in the lab, and a table buried in the article does not travel with the data.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"Table 1. Analyzed Individuals and Well-Imputed Autosomal Genetic Variants","why":"Variable definitions are provided inside the article (Table 1), but no separate documentation file is mentioned as traveling with the data. [majority verdict 'partial' (3/5 passes agreed)]","gain":0.0,"priority":"important","scored":false},{"key":"i_qualified_references","dimension":"I","label":"Identifiers for the resources the data depend on","action":"Cite by identifier every resource the data depend on — the source datasets' accessions, the reference build (GRCh38 / GCA_000001405.28), the cohort application number, the code DOI — and register those relations on the dataset record (IsDerivedFrom, IsSupplementTo). A name is not a link: it cannot be resolved, versioned, or followed by a machine.","anchors":["yes","partial","no"],"verdict":"no","current":0.0,"evidence":null,"why":"No identifier for any external resource (other than the paper's own dataset) is provided; references are bare names or citations. [majority verdict 'no' (3/5 passes agreed)]","gain":0.0,"priority":"useful","scored":false},{"key":"a_timeline_retention","dimension":"A","label":"Availability timing & retention","action":"State when the data become available AND how long they will be retained — cite the repository's preservation policy. NIH DMS Element 4 asks for both; most papers give neither.","anchors":["yes","partial","no"],"verdict":"partial","current":0.5,"evidence":"GWAS summary statistics are available (upon publication)","why":"The paper states when the data become available (upon publication) but does not commit to how long they persist.","gain":0.0,"priority":"useful","scored":false}],"suggestions":["Attach a standard, machine-readable open licence to the deposit — CC0 or CC BY, which is what Horizon Europe and most funders expect — and print the licence identifier in the paper. 'Free to use' is not a licence: it grants nothing a reuser's institution can rely on.","Remove the precondition or justify it. Release the data at publication with no embargo, no registration wall, and no approval step — NIH's zero-embargo public- access rule (NOT-OD-25-101) has already made 'available at publication' the federal baseline for the article; the data should not lag behind it. For clinical / human-subjects data, deposit in dbGaP or the European Genome-phenome Archive (EGA).","Release the data in an open, community-standard format (CSV/TSV, JSON, HDF5, NetCDF, FASTQ, VCF, NIfTI…) instead of — or alongside — any proprietary or instrument-native format, and name the format in the paper. A dataset that needs a €2,000 licence to open is not reusable.","Cite the dataset in the reference list like a publication — creator, year, title, repository, DOI/accession — and cite it in-text where it is used. Only a reference- list entry is machine-readable to Crossref/DataCite, and only a citation lets the data earn credit. Cite the clinical / human-subjects repository accession (e.g. from dbGaP or the European Genome-phenome Archive (EGA)) in the reference list.","State the access level in words, using the standard vocabulary: 'These data are open access' / 'These data are controlled access'. A reader — and a harvester — should not have to infer the access level from the presence of a download link."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v8","fulltext_source":"epmc_xml"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v8","fair_fulltext_source":"epmc_xml","fair_has_llm":true,"fair_computed_at":"2026-07-20T13:45:19.885606Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}