{"doi":"10.1101/2021.09.22.21263909","title":"Pervasive Downward Bias in Estimates of Liability Scale Heritability in GWAS Meta-Analysis: A Simple Solution","abstract":"Abstract SNP heritability is a fundamental quantity in the genetic analysis of complex traits. For binary phenotypes, in which the continuous distribution of risk in the population is unobserved, observed-scale heritabilities must be transformed to the more interpretable liability-scale. We demonstrate here that the field standard approach for performing the liability conversion can downwardly bias estimates by as much as ∼20% in simulation and ∼30% in real data. These attenuated estimates stem from the standard approach failing to appropriately account for varying levels of ascertainment across the cohorts comprising the meta-analysis. We formally derive a simple procedure for incorporating cohort-specific ascertainment based on the summation of effective sample sizes across the contributing cohorts, and confirm via simulation that it produces unbiased estimates of liability-scale heritability.","journal":"medRxiv","year":2021,"id":214243,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9421,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":267892,"name":"Javier de la Fuente","orcid":"0000-0001-8352-7104","position":1,"is_corresponding":false},{"id":5264,"name":"Michel G. Nivard","orcid":"0000-0003-2015-1888","position":2,"is_corresponding":false},{"id":228674,"name":"Elliot M. Tucker–Drob","orcid":"0000-0001-5599-6237","position":3,"is_corresponding":false},{"id":52335,"name":"Andrew D. Grotzinger","orcid":"0000-0001-7852-9244","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:52:46.604690Z","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":[]}