{"doi":"10.1002/mgg3.1248","title":"A polygenic biomarker to identify patients with severe hypercholesterolemia of polygenic origin","abstract":"Abstract Background Severe hypercholesterolemia (HC, LDL‐C > 4.9 mmol/L) affects over 30 million people worldwide. In this study, we validated a new polygenic risk score (PRS) for LDL‐C. Methods Summary statistics from the Global Lipid Genome Consortium and genotype data from two large populations were used. Results A 36‐SNP PRS was generated using data for 2,197 white Americans. In a replication cohort of 4,787 Finns, the PRS was strongly associated with the LDL‐C trait and explained 8% of its variability ( p = 10 –41 ). After risk categorization, the risk of having HC was higher in the high‐ versus low‐risk group (RR = 4.17, p < 1 × 10 −7 ). Compared to a 12‐SNP LDL‐C raising score (currently used in the United Kingdom), the PRS explained more LDL‐C variability (8% vs. 6%). Among Finns with severe HC, 53% (66/124) versus 44% (55/124) were classified as high risk by the PRS and LDL‐C raising score, respectively. Moreover, 54% of individuals with severe HC defined as low risk by the LDL‐C raising score were reclassified to intermediate or high risk by the new PRS. Conclusion The new PRS has a better predictive role in identifying HC of polygenic origin compared to the currently available method and can better stratify patients into diagnostic and therapeutic algorithms.","journal":"Molecular Genetics & Genomic Medicine","year":2020,"id":79372,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.881,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260579,"name":"Clive Hoggart","orcid":"0000-0002-6875-6993","position":1,"is_corresponding":false},{"id":412956,"name":"Marjo-Riitta Järvelin","orcid":null,"position":2,"is_corresponding":false},{"id":412173,"name":"Karl‐Heinz Herzig","orcid":"0000-0003-4460-2604","position":3,"is_corresponding":false},{"id":3514,"name":"Michael J.E. Sternberg","orcid":"0000-0002-1884-5445","position":4,"is_corresponding":false},{"id":412174,"name":"Alessia David","orcid":"0000-0001-8687-024X","position":5,"is_corresponding":false},{"id":412172,"name":"Luis G. Leal","orcid":"0009-0000-6862-1792","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-18T21:50:33.748601Z","pmid":"32307928","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":[]}