{"doi":"10.17615/msaw-3g92","title":"Genome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels","abstract":"Variants associated with blood lipid levels may be population-specific. To identify low-frequency variants associated with this phenotype, population-specific reference panels may be used. Here we impute nine large Dutch biobanks (~35,000 samples) with the population-specific reference panel created by the Genome of the Netherlands Project and perform association testing with blood lipid levels. We report the discovery of five novel associations at four loci (P value <6.61 × 10−4), including a rare missense variant in ABCA6 (rs77542162, p.Cys1359Arg, frequency 0.034), which is predicted to be deleterious. The frequency of this ABCA6 variant is 3.65-fold increased in the Dutch and its effect (βLDL-C=0.135, βTC=0.140) is estimated to be very similar to those observed for single variants in well-known lipid genes, such as LDLR. Frequencies of rare variants fluctuate over populations, hampering gene discovery. Here the authors use a population-specific reference panel, the Genome of the Netherlands, to discover four novel loci involved in lipid metabolism, including an exonic variant in ABCA6.","journal":"Digital Commons@Becker (Washington University School of Medicine)","year":2020,"id":140758,"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":0.8463,"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":299819,"name":"Patrick Deelen","orcid":"0000-0002-5654-3966","position":1,"is_corresponding":false},{"id":606098,"name":"David J. van Enckevort","orcid":null,"position":2,"is_corresponding":false},{"id":21709,"name":"Irene Mateo Leach","orcid":"0009-0008-8017-5877","position":3,"is_corresponding":false},{"id":24655,"name":"Gina M. Peloso","orcid":"0000-0002-5355-8636","position":4,"is_corresponding":false},{"id":21696,"name":"Mary F. Feitosa","orcid":"0000-0002-0933-2410","position":5,"is_corresponding":false},{"id":21780,"name":"Aaron Isaacs","orcid":"0000-0001-5037-4834","position":6,"is_corresponding":false},{"id":606099,"name":"Freerk van Dijk","orcid":null,"position":7,"is_corresponding":false},{"id":21890,"name":"Albert Hofman","orcid":"0000-0002-9865-121X","position":8,"is_corresponding":false},{"id":69282,"name":"Alexandros Kanterakis","orcid":"0000-0003-4276-0115","position":9,"is_corresponding":false},{"id":5395,"name":"Brenda W.J.H. Penninx","orcid":"0000-0001-7779-9672","position":10,"is_corresponding":false},{"id":596870,"name":"Ben A. Oostra","orcid":null,"position":11,"is_corresponding":false},{"id":5392,"name":"Eco J. C. de Geus","orcid":"0000-0001-6022-2666","position":12,"is_corresponding":false},{"id":605558,"name":"Lennart C. Karssen","orcid":"0000-0002-1959-342X","position":13,"is_corresponding":false},{"id":5313,"name":"Gonneke Willemsen","orcid":"0000-0003-3755-0236","position":14,"is_corresponding":false},{"id":606100,"name":"Iris Postmus","orcid":null,"position":15,"is_corresponding":false},{"id":5251,"name":"Hamdi Mbarek","orcid":"0000-0002-1108-0371","position":16,"is_corresponding":false},{"id":108708,"name":"Jennifer E. Huffman","orcid":"0000-0002-9672-2491","position":17,"is_corresponding":false},{"id":108718,"name":"Traci M. Bartz","orcid":"0000-0003-3403-8763","position":18,"is_corresponding":false},{"id":529469,"name":"van Leeuwen, Elisabeth M.","orcid":null,"position":19,"is_corresponding":false},{"id":55334,"name":"Peter K. 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Francioli","orcid":"0000-0002-3039-8895","position":28,"is_corresponding":false},{"id":21748,"name":"Joris Deelen","orcid":"0000-0003-4483-3701","position":29,"is_corresponding":false},{"id":21721,"name":"Stella Trompet","orcid":"0000-0001-5006-0528","position":30,"is_corresponding":false},{"id":38662,"name":"Oscar H. Franco","orcid":"0000-0002-4606-4929","position":31,"is_corresponding":false},{"id":272377,"name":"Sara L. 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