{"doi":"10.1371/journal.pgen.0020123","title":"Family-Based versus Unrelated Case-Control Designs for Genetic Associations","abstract":"The most simple and commonly used approach for genetic associations is the case-control study design of unrelated people. This design is susceptible to population stratification. This problem is obviated in family-based studies, but it is usually difficult to accumulate large enough samples of well-characterized families. We addressed empirically whether the two designs give similar estimates of association in 93 investigations where both unrelated case-control and family-based designs had been employed. Estimated odds ratios differed beyond chance between the two designs in only four instances (4%). The summary relative odds ratio (ROR) (the ratio of odds ratios obtained from unrelated case-control and family-based studies) was close to unity (0.96 [95% confidence interval, 0.91-1.01]). There was no heterogeneity in the ROR across studies (amount of heterogeneity beyond chance I(2) = 0%). Differences on whether results were nominally statistically significant (p < 0.05) or not with the two designs were common (opposite classification rates 14% and 17%); this reflected largely differences in power. Conclusions were largely similar in diverse subgroup analyses. Unrelated case-control and family-based designs give overall similar estimates of association. We cannot rule out rare large biases or common small biases.","journal":"PLoS Genetics","year":2006,"id":3844,"datarank":2.842550643208347,"base_score":4.23410650459726,"endowment":4.23410650459726,"self_citation_contribution":0.635115975689589,"citation_network_contribution":2.207434667518758,"self_endowment_contribution":0.635115975689589,"citer_contribution":2.207434667518758,"corpus_percentile":null,"corpus_rank":null,"citation_count":68,"citer_count":62,"citers_with_citation_signal":46,"citers_with_endowment":46,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0458,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2006-08-11","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11861,"name":"Thomas A. Trikalinos","orcid":"0000-0002-3990-1848","position":1,"is_corresponding":false},{"id":6209,"name":"Georgia Salanti","orcid":"0000-0002-3830-8508","position":2,"is_corresponding":false},{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":3,"is_corresponding":false},{"id":2427,"name":"Evangelos Evangelou","orcid":"0000-0002-5488-2999","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"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":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":[]}