{"doi":"10.1101/2022.01.06.22268853","title":"Capturing additional genetic risk from family history for improved polygenic risk prediction","abstract":"ABSTRACT Family history of complex traits may reflect transmitted rare pathogenic variants, intra-familial shared exposures to environmental and lifestyle factors, as well as a common genetic predisposition. We developed a latent factor model to quantify trait heritability in excess of that captured by a common variant-based polygenic risk score, but inferable from family history. For 941 children in the Avon Longitudinal Study of Parents and Children cohort, a joint predictor combining a polygenic risk score for height and mid-parental height was able to explain ∼55% of the total variance in sex-adjusted adult height z-scores, close to the estimated heritability. Marginal yet consistent risk prediction improvements were also achieved among ∼400,000 European ancestry participants for 11 complex diseases in the UK Biobank. Our work showcases a paradigm for risk calculation, and supports incorporation of family history into polygenic risk score-based genetic risk prediction models.","journal":"medRxiv","year":2022,"id":299711,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9386,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":267237,"name":"Vincenzo Forgetta","orcid":"0000-0002-6061-4720","position":1,"is_corresponding":false},{"id":37303,"name":"J. Brent Richards","orcid":"0000-0002-3746-9086","position":2,"is_corresponding":false},{"id":304553,"name":"Celia M.T. Greenwood","orcid":"0000-0002-2427-5696","position":3,"is_corresponding":false},{"id":269890,"name":"Tianyuan Lu","orcid":"0000-0002-5664-5698","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","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":[]}