{"doi":"10.17615/sbz9-wg52","title":"Association of Low-Frequency and Rare Coding-Sequence Variants with Blood Lipids and Coronary Heart Disease in 56,000 Whites and Blacks","abstract":"Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the “Exome Array” to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121∗], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.","journal":"UNC Libraries","year":2020,"id":139046,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"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":24976,"name":"Rebecca D. Jackson","orcid":"0000-0003-1682-5544","position":1,"is_corresponding":false},{"id":601845,"name":"Valeska Redon","orcid":null,"position":2,"is_corresponding":false},{"id":24655,"name":"Gina M. Peloso","orcid":"0000-0002-5355-8636","position":3,"is_corresponding":false},{"id":17626,"name":"Joshua C. Bis","orcid":"0000-0002-3409-1110","position":4,"is_corresponding":false},{"id":601846,"name":"Arend Voorman","orcid":null,"position":5,"is_corresponding":false},{"id":74975,"name":"Rachel H. Mackey","orcid":"0000-0001-6088-2664","position":6,"is_corresponding":false},{"id":51216,"name":"Alanna C. Morrison","orcid":"0000-0001-6381-4296","position":7,"is_corresponding":false},{"id":21696,"name":"Mary F. Feitosa","orcid":"0000-0002-0933-2410","position":8,"is_corresponding":false},{"id":601847,"name":"Jacy R. Crosby","orcid":null,"position":9,"is_corresponding":false},{"id":296354,"name":"Sumeet A. Khetarpal","orcid":"0009-0000-8269-6889","position":10,"is_corresponding":false},{"id":175,"name":"Gail Davies","orcid":"0000-0003-1120-7026","position":11,"is_corresponding":false},{"id":480593,"name":"Kelli K. Ryckman","orcid":"0000-0002-9496-4147","position":12,"is_corresponding":false},{"id":601152,"name":"Paolo Zanoni","orcid":"0000-0001-9397-1989","position":13,"is_corresponding":false},{"id":11265,"name":"Christopher S. Carlson","orcid":"0000-0003-0561-3538","position":14,"is_corresponding":false},{"id":21780,"name":"Aaron Isaacs","orcid":"0000-0001-5037-4834","position":15,"is_corresponding":false},{"id":240626,"name":"Albert V. Smith","orcid":"0000-0003-1942-5845","position":16,"is_corresponding":false},{"id":108708,"name":"Jennifer E. Huffman","orcid":"0000-0002-9672-2491","position":17,"is_corresponding":false},{"id":231458,"name":"Nathan O. Stitziel","orcid":"0000-0002-4963-8211","position":18,"is_corresponding":false},{"id":24941,"name":"Paul L. Auer","orcid":"0000-0003-1735-8044","position":19,"is_corresponding":false},{"id":11275,"name":"Ani Manichaikul","orcid":"0000-0002-5998-795X","position":20,"is_corresponding":false},{"id":24948,"name":"Jennifer A. Brody","orcid":"0000-0001-8509-148X","position":21,"is_corresponding":false},{"id":262579,"name":"Brian J. Davis","orcid":"0000-0002-8288-1096","position":22,"is_corresponding":false},{"id":256103,"name":"Megan L. Grove","orcid":"0000-0001-6764-2508","position":23,"is_corresponding":false},{"id":601153,"name":"Kim Lawson","orcid":"0000-0002-5458-1897","position":24,"is_corresponding":false},{"id":44926,"name":"Serkalem Demissie","orcid":"0000-0002-8009-0987","position":25,"is_corresponding":false},{"id":601154,"name":"Jóhanna Jakobsdóttir","orcid":"0000-0002-8019-9683","position":26,"is_corresponding":false},{"id":71310,"name":"Jennifer G. Robinson","orcid":"0000-0002-4432-4352","position":27,"is_corresponding":false},{"id":520135,"name":"Peters, Ulrike","orcid":null,"position":28,"is_corresponding":false},{"id":267326,"name":"David S. Siscovick","orcid":"0000-0003-0461-175X","position":29,"is_corresponding":false},{"id":413961,"name":"Aron Y. Joon","orcid":"0000-0003-2615-2179","position":30,"is_corresponding":false},{"id":17640,"name":"Myriam Fornage","orcid":"0000-0003-0677-8158","position":31,"is_corresponding":false},{"id":130818,"name":"Kurt Lohman","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:17:06.651725Z","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":[]}