{"doi":"10.1093/aje/kwi165","title":"CTLA-4 Gene Polymorphisms and Susceptibility to Type 1 Diabetes Mellitus: A HuGE Review and Meta-Analysis","abstract":"The authors performed a meta-analysis of 33 studies examining the association of type 1 diabetes mellitus with polymorphisms in the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene, including the A49G (29 comparisons), C(-318)T (three comparisons), and (AT)n microsatellite (six comparisons) polymorphisms. The studies included 5,637 cases of type 1 diabetes and 6,759 controls (4,775 and 5,829, respectively, for analysis of the A49G polymorphism). The random-effects odds ratio for the *G (Ala) allele versus the *A (Thr) allele was 1.45 (95% confidence interval (CI): 1.28, 1.65), with significant between-study heterogeneity (p < 0.001). The effect size tended to be higher in type 1 diabetes cases with age of onset <20 years (odds ratio (OR) = 1.61), and there was a significant association between the presence of glutamic acid decarboxylase-65 autoantibodies and the *G allele among type 1 diabetes cases (OR = 1.49). Larger studies showed more conservative results (p = 0.011). After exclusion of studies with fewer than 150 subjects and studies with significant deviation from Hardy-Weinberg equilibrium in the controls, the summary odds ratio was 1.40 (95% CI: 1.28, 1.54). Available data showed no strong association for the 106-base-pair allele of the microsatellite polymorphism (OR = 0.99, 95% CI: 0.64, 1.55) or the *T allele of the C(-318)T polymorphism (OR = 0.92, 95% CI: 0.45, 1.89). This meta-analysis demonstrates that the CTLA-4*G genotype is associated with type 1 diabetes.","journal":"American Journal of Epidemiology","year":2005,"id":3874,"datarank":0.7242470605953454,"base_score":4.8283137373023015,"endowment":4.8283137373023015,"self_citation_contribution":0.7242470605953454,"citation_network_contribution":0.0,"self_endowment_contribution":0.7242470605953454,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":124,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0568,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2005-07-01","fair_score":18.75,"fair_percentile":1.7590149516270888,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":1,"is_corresponding":false},{"id":15421,"name":"Fotini K. Kavvoura","orcid":null,"position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"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":32.5,"fair_a":30.0,"fair_i":12.5,"fair_r":0.0,"fair_zscore":-2.3936,"fair_rationale":{"fair_score":18.75,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":32.5,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"datacite=0, pmcid=False, pmid=False","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper only reports aggregated statistical results and does not provide any accompanying machine-readable metadata (e.g., study-level data in a structured format)."}]},"A":{"name":"Accessible","score":30.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.0,"signal":null,"rationale":"The text contains no statement about how the underlying data or code can be accessed, nor a link to any repository."}]},"I":{"name":"Interoperable","score":12.5,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper uses standard genetic nomenclature and effect-size metrics (OR, CI), but lacks reference to any standardized ontologies, controlled vocabularies, or globally unique identifiers for the data."}]},"R":{"name":"Reusable","score":0.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"not a dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.0,"signal":null,"rationale":"No data-availability statement, license, or provisions for reproducibility are mentioned, and the text does not indicate that the study data or code are preserved for reuse."}]}},"suggestions":["Provide the full study-level data (e.g., counts, ORs, CIs) in a machine-readable format (CSV, JSON) and deposit it in a public repository like Zenodo or Figshare.","Include a clear data-availability statement with a persistent identifier (e.g., DOI) and a license (e.g., CC0 or CC-BY 4.0) in the paper.","Use standardized identifiers for genes (e.g., HGNC symbols) and polymorphisms (e.g., dbSNP rsIDs) and reference controlled vocabularies for study characteristics (e.g., age, ethnicity) to enhance interoperability.","Create a reproducible analysis pipeline (e.g., R script, Jupyter notebook) and link it from the paper to enable verification and reuse of the meta-analysis.","Add explicit metadata about inclusion/exclusion criteria and study-level quality metrics (e.g., Hardy-Weinberg p-values) in a structured, queryable format."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v1","fulltext_source":"abstract_only"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v1","fair_fulltext_source":"abstract_only","fair_has_llm":true,"fair_computed_at":"2026-06-14T20:31:34.444188Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}