{"entity": "publication", "iuid": "ea64623217244bc2bcf2b887b655475c", "timestamp": "2026-03-12T19:31:19.106Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea64623217244bc2bcf2b887b655475c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea64623217244bc2bcf2b887b655475c"}}, "title": "PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study.", "authors": [{"family": "Schmidt", "given": "Amand F", "initials": "AF"}, {"family": "Swerdlow", "given": "Daniel I", "initials": "DI"}, {"family": "Holmes", "given": "Michael V", "initials": "MV"}, {"family": "Patel", "given": "Riyaz S", "initials": "RS"}, {"family": "Fairhurst-Hunter", "given": "Zammy", "initials": "Z"}, {"family": "Lyall", "given": "Donald M", "initials": "DM"}, {"family": "Hartwig", "given": "Fernando Pires", "initials": "FP"}, {"family": "Horta", "given": "Bernardo Lessa", "initials": "BL"}, {"family": "Hypp\u00f6nen", "given": "Elina", "initials": "E"}, {"family": "Power", "given": "Christine", "initials": "C"}, {"family": "Moldovan", "given": "Max", "initials": "M"}, {"family": "van Iperen", "given": "Erik", "initials": "E"}, {"family": "Hovingh", "given": "G Kees", "initials": "GK"}, {"family": "Demuth", "given": "Ilja", "initials": "I"}, {"family": "Norman", "given": "Kristina", "initials": "K"}, {"family": "Steinhagen-Thiessen", "given": "Elisabeth", "initials": "E"}, {"family": "Demuth", "given": "Juri", "initials": "J"}, {"family": "Bertram", "given": "Lars", "initials": "L"}, {"family": "Liu", "given": "Tian", "initials": "T"}, {"family": "Coassin", "given": "Stefan", "initials": "S"}, {"family": "Willeit", "given": "Johann", "initials": "J"}, {"family": "Kiechl", "given": "Stefan", "initials": "S"}, {"family": "Willeit", "given": "Karin", "initials": "K"}, {"family": "Mason", "given": "Dan", "initials": "D"}, {"family": "Wright", "given": "John", "initials": "J"}, {"family": "Morris", "given": "Richard", "initials": "R"}, {"family": "Wanamethee", "given": "Goya", "initials": "G"}, {"family": "Whincup", "given": "Peter", "initials": "P"}, {"family": "Ben-Shlomo", "given": "Yoav", "initials": "Y"}, {"family": "McLachlan", "given": "Stela", "initials": "S"}, {"family": "Price", "given": "Jackie F", "initials": "JF"}, {"family": "Kivimaki", "given": "Mika", "initials": "M"}, {"family": "Welch", "given": "Catherine", "initials": "C"}, {"family": "Sanchez-Galvez", "given": "Adelaida", "initials": "A"}, {"family": "Marques-Vidal", "given": "Pedro", "initials": "P"}, {"family": "Nicolaides", "given": "Andrew", "initials": "A"}, {"family": "Panayiotou", "given": "Andrie G", "initials": "AG"}, {"family": "Onland-Moret", "given": "N Charlotte", "initials": "NC"}, {"family": "van der Schouw", "given": "Yvonne T", "initials": "YT"}, {"family": "Matullo", "given": "Giuseppe", "initials": "G"}, {"family": "Fiorito", "given": "Giovanni", "initials": "G"}, {"family": "Guarrera", "given": "Simonetta", "initials": "S"}, {"family": "Sacerdote", "given": "Carlotta", "initials": "C"}, {"family": "Wareham", "given": "Nicholas J", "initials": "NJ"}, {"family": "Langenberg", "given": "Claudia", "initials": "C"}, {"family": "Scott", "given": "Robert", "initials": "R"}, {"family": "Luan", "given": "Jian'an", "initials": "J"}, {"family": "Bobak", "given": "Martin", "initials": "M"}, {"family": "Malyutina", "given": "Sofia", "initials": "S"}, {"family": "Paj\u0105k", "given": "Andrzej", "initials": "A"}, {"family": "Kubinova", "given": "Ruzena", "initials": "R"}, {"family": "Tamosiunas", "given": "Abdonas", "initials": "A"}, {"family": "Pikhart", "given": "Hynek", "initials": "H"}, {"family": "Husemoen", "given": "Lise Lotte Nystrup", "initials": "LL"}, {"family": "Grarup", "given": "Niels", "initials": "N"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Linneberg", "given": "Allan", "initials": "A"}, {"family": "Simonsen", "given": "Kenneth Starup", "initials": "KS"}, {"family": "Cooper", "given": "Jackie", "initials": "J"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "Brilliant", "given": "Murray", "initials": "M"}, {"family": "Kitchner", "given": "Terrie", "initials": "T"}, {"family": "Hakonarson", "given": "Hakon", "initials": "H"}, {"family": "Carrell", "given": "David S", "initials": "DS"}, {"family": "McCarty", "given": "Catherine A", "initials": "CA"}, {"family": "Kirchner", "given": "H Lester", "initials": "HL"}, {"family": "Larson", "given": "Eric B", "initials": "EB"}, {"family": "Crosslin", "given": "David R", "initials": "DR"}, {"family": "de Andrade", "given": "Mariza", "initials": "M"}, {"family": "Roden", "given": "Dan M", "initials": "DM"}, {"family": "Denny", "given": "Joshua C", "initials": "JC"}, {"family": "Carty", "given": "Cara", "initials": "C"}, {"family": "Hancock", "given": "Stephen", "initials": "S"}, {"family": "Attia", "given": "John", "initials": "J"}, {"family": "Holliday", "given": "Elizabeth", "initials": "E"}, {"family": "O'Donnell", "given": "Martin", "initials": "M"}, {"family": "Yusuf", "given": "Salim", "initials": "S"}, {"family": "Chong", "given": "Michael", "initials": "M"}, {"family": "Pare", "given": "Guillaume", "initials": "G"}, {"family": "van der Harst", "given": "Pim", "initials": "P"}, {"family": "Said", "given": "M Abdullah", "initials": "MA"}, {"family": "Eppinga", "given": "Ruben N", "initials": "RN"}, {"family": "Verweij", "given": "Niek", "initials": "N"}, {"family": "Snieder", "given": "Harold", "initials": "H"}, {"family": "LifeLines Cohort study group", "given": null, "initials": null}, {"family": "Christen", "given": "Tim", "initials": "T"}, {"family": "Mook-Kanamori", "given": "Dennis O", "initials": "DO"}, {"family": "Gustafsson", "given": "Stefan", "initials": "S"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Pazoki", "given": "Raha", "initials": "R"}, {"family": "Franco", "given": "Oscar", "initials": "O"}, {"family": "Hofman", "given": "Albert", "initials": "A"}, {"family": "Uitterlinden", "given": "Andre", "initials": "A"}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Teumer", "given": "Alexander", "initials": "A"}, {"family": "Baumeister", "given": "Sebastian", "initials": "S"}, {"family": "D\u00f6rr", "given": "Marcus", "initials": "M"}, {"family": "Lerch", "given": "Markus M", "initials": "MM"}, {"family": "V\u00f6lker", "given": "Uwe", "initials": "U"}, {"family": "V\u00f6lzke", "given": "Henry", "initials": "H"}, {"family": "Ward", "given": "Joey", "initials": "J"}, {"family": "Pell", "given": "Jill P", "initials": "JP"}, {"family": "Smith", "given": "Daniel J", "initials": "DJ"}, {"family": "Meade", "given": "Tom", "initials": "T"}, {"family": "Maitland-van der Zee", "given": "Anke H", "initials": "AH"}, {"family": "Baranova", "given": "Ekaterina V", "initials": "EV"}, {"family": "Young", "given": "Robin", "initials": "R"}, {"family": "Ford", "given": "Ian", "initials": "I"}, {"family": "Campbell", "given": "Archie", "initials": "A"}, {"family": "Padmanabhan", "given": "Sandosh", "initials": "S"}, {"family": "Bots", "given": "Michiel L", "initials": "ML"}, {"family": "Grobbee", "given": "Diederick E", "initials": "DE"}, {"family": "Froguel", "given": "Philippe", "initials": "P"}, {"family": "Thuillier", "given": "Doroth\u00e9e", "initials": "D"}, {"family": "Balkau", "given": "Beverley", "initials": "B"}, {"family": "Bonnefond", "given": "Am\u00e9lie", "initials": "A"}, {"family": "Cariou", "given": "Bertrand", "initials": "B"}, {"family": "Smart", "given": "Melissa", "initials": "M"}, {"family": "Bao", "given": "Yanchun", "initials": "Y"}, {"family": "Kumari", "given": "Meena", "initials": "M"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Ridker", "given": "Paul M", "initials": "PM"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Reiner", "given": "Alex P", "initials": "AP"}, {"family": "Lange", "given": "Leslie A", "initials": "LA"}, {"family": "Ritchie", "given": "Marylyn D", "initials": "MD"}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW"}, {"family": "Casas", "given": "Juan-Pablo", "initials": "JP"}, {"family": "Keating", "given": "Brendan J", "initials": "BJ"}, {"family": "Preiss", "given": "David", "initials": "D"}, {"family": "Hingorani", "given": "Aroon D", "initials": "AD"}, {"family": "UCLEB consortium", "given": null, "initials": null}, {"family": "Sattar", "given": "Naveed", "initials": "N"}], "type": "journal article", "published": "2017-02-00", "journal": {"volume": "5", "issn": "2213-8595", "issue": "2", "pages": "97-105", "title": "Lancet Diabetes Endocrinol", "issn-l": "2213-8587"}, "abstract": "Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.\n\nIn this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.\n\nData were available for more than 550\u2008000 individuals and 51\u2008623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0\u00b709 mmol/L, 95% CI 0\u00b702 to 0\u00b715), bodyweight (1\u00b703 kg, 0\u00b724 to 1\u00b782), waist-to-hip ratio (0\u00b7006, 0\u00b7003 to 0\u00b7010), and an odds ratio for type diabetes of 1\u00b729 (1\u00b711 to 1\u00b750). Based on the collected data, we did not identify associations with HbA1c (0\u00b703%, -0\u00b701 to 0\u00b708), fasting insulin (0\u00b700%, -0\u00b706 to 0\u00b707), and BMI (0\u00b711 kg/m(2), -0\u00b709 to 0\u00b730).\n\nPCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins.\n\nBritish Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.", "doi": "10.1016/S2213-8587(16)30396-5", "pmid": "27908689", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2213-8587(16)30396-5"}, {"db": "pmc", "key": "PMC5266795"}], "notes": [], "created": "2017-05-03T12:59:53.796Z", "modified": "2024-01-16T13:48:48.535Z"}