1. Ktisis Cyprus University of Technology
  2. Cyprus University of Technology (Research Output)
  3. Άρθρα/Articles
Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.14279/10079
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dc.contributor.authorSchmidt, Amand F.-
dc.contributor.authorSwerdlow, Daniel I.-
dc.contributor.authorHolmes, Michael Vaclav-
dc.contributor.authorPatel, Riyaz Suleman-
dc.contributor.authorFairhurst-Hunter, Zammy-
dc.contributor.authorLyall, Donald M.-
dc.contributor.authorHartwig, Fernando Pires-
dc.contributor.authorHorta, Bernardo Lessa-
dc.contributor.authorHyppönen, Elina-
dc.contributor.authorPower, Chris-
dc.contributor.authorMoldovan, Max V.-
dc.contributor.authorLind, Lars-
dc.contributor.authorIngelsson, Erik-
dc.contributor.authorPazoki, Raha-
dc.contributor.authorFranco, Oscar H.-
dc.contributor.authorHofman, Albert-
dc.contributor.authorUitterlinden, André G.-
dc.contributor.authorDehghan, Abbas-
dc.contributor.authorTeumer, Alexander-
dc.contributor.authorBaumeister, Sebastian Edgar-
dc.contributor.authorPell, Jill P.-
dc.contributor.authorMahajan, Anubha-
dc.contributor.authorDörr, Marcus-
dc.contributor.authorLerch, Markus M.-
dc.contributor.authorVölker, Uwe U.-
dc.contributor.authorSmith, Daniel J.-
dc.contributor.authorMeade, Tom W.-
dc.contributor.authorMaitland-van Der Zee, Anke Hilse-
dc.contributor.authorBaranova, Ekaterina V.-
dc.contributor.authorYoung, Robin-
dc.contributor.authorFord, Ian-
dc.contributor.authorCampbell, Archie-
dc.contributor.authorRidker, Paul M.-
dc.contributor.authorVan Iperen, Erik P.A-
dc.contributor.authorPadmanabhan, Sandosh-
dc.contributor.authorBots, Michiel L.-
dc.contributor.authorGrobbee, Diederick E.-
dc.contributor.authorFroguel, Philippe H.-
dc.contributor.authorThuillier, Dorothée-
dc.contributor.authorBalkau, Beverley J.-
dc.contributor.authorBonnefond, Amélie-
dc.contributor.authorCariou, Bertrand-
dc.contributor.authorSmart, Melissa C.-
dc.contributor.authorChasman, Daniel I.-
dc.contributor.authorBao, Yanchun-
dc.contributor.authorHovingh, Gerald Kees-
dc.contributor.authorKumari, Meena-
dc.contributor.authorReiner, Alexander Paul-
dc.contributor.authorLange, Leslie A.-
dc.contributor.authorRitchie, Marylyn D.-
dc.contributor.authorAsselbergs, Folkert W.-
dc.contributor.authorCasas, Juan Pablo-
dc.contributor.authorKeating, Brendan J.-
dc.contributor.authorDemuth, Ilja-
dc.contributor.authorMarques-Vidal, Pedro-
dc.contributor.authorPreiss, David J.-
dc.contributor.authorHingorani, Aroon D.-
dc.contributor.authorSattar, Naveed A.-
dc.contributor.authorNorman, Kristina-
dc.contributor.authorSteinhagen-Thiessen, Elisabeth-
dc.contributor.authorDemuth, Juri-
dc.contributor.authorBertram, Lars-
dc.contributor.authorLiu, Tian-
dc.contributor.authorCoassin, Stefan-
dc.contributor.authorWilleit, Johann-
dc.contributor.authorNicolaides, Andrew N.-
dc.contributor.authorKiechl, Stefan-
dc.contributor.authorWilleit, Karin-
dc.contributor.authorMason, Dan-
dc.contributor.authorWright, John P.-
dc.contributor.authorMorris, Richard W.-
dc.contributor.authorWanamethee, Goya-
dc.contributor.authorWhincup, Peter Hynes-
dc.contributor.authorBen-Shlomo, Yoav-
dc.contributor.authorMcLachlan, Stela-
dc.contributor.authorPrice, Jackie F.-
dc.contributor.authorPanayiotou, Andrie G.-
dc.contributor.authorKivimaki, Mika-
dc.contributor.authorWelch, Catherine A.-
dc.contributor.authorSanchez-Galvez, Adelaida-
dc.contributor.authorOnland-Moret, N. Charlotte-
dc.contributor.authorVan der Schouw, Y. T.-
dc.contributor.authorMatullo, Giuseppe-
dc.contributor.authorFiorito, Giovanni-
dc.contributor.authorGuarrera, Simonetta-
dc.contributor.authorSacerdote, Carlotta-
dc.contributor.authorWareham, Nicholas J.J.-
dc.contributor.authorLarson, Eric B.-
dc.contributor.authorLangenberg, Claudia-
dc.contributor.authorScott, Robert A.-
dc.contributor.authorLuan, Jian'an-
dc.contributor.authorBobak, Martin-
dc.contributor.authorMalyutina, Sofia-
dc.contributor.authorPająk, Andrzej-
dc.contributor.authorKubinova, Růžena-
dc.contributor.authorTamosiunas, Abdonas-
dc.contributor.authorPikhart, Hynek-
dc.contributor.authorHusemoen, Lise Lotte Nystrup-
dc.contributor.authorCrosslin, David R.-
dc.contributor.authorGrarup, Niels-
dc.contributor.authorPedersen, Oluf Borbye Orbye-
dc.contributor.authorHansen, Torben Froestrup-
dc.contributor.authorLinneberg, Allan-
dc.contributor.authorSimonsen, Kenneth Starup-
dc.contributor.authorCooper, Jackie A.-
dc.contributor.authorHumphries, Steve Eric-
dc.contributor.authorBrilliant, Murray H.-
dc.contributor.authorKitchner, Terrie E.-
dc.contributor.authorHakonarson, Håkon H.-
dc.contributor.authorDe Andrade, Mariza De-
dc.contributor.authorCarrell, David S.-
dc.contributor.authorMcCarty, Catherine A.-
dc.contributor.authorKirchner, H. Lester-
dc.contributor.authorRoden, Dan M.-
dc.contributor.authorDenny, Joshua C.-
dc.contributor.authorCarty, Cara L.-
dc.contributor.authorHancock, Stephen John-
dc.contributor.authorAttia, John-
dc.contributor.authorHolliday, Elizabeth G.-
dc.contributor.authorO'Donnell, Martin-
dc.contributor.authorVölzke, Henry-
dc.contributor.authorYusuf, Salim-
dc.contributor.authorChong, Michael-
dc.contributor.authorPare, Guillaume-
dc.contributor.authorVan Der Harst, Pim-
dc.contributor.authorSaid, Michael Abdullah-
dc.contributor.authorEppinga, Ruben N.-
dc.contributor.authorVerweij, Niek-
dc.contributor.authorSnieder, Harold-
dc.contributor.authorChristen, Tim-
dc.contributor.authorMook-Kanamori, Dennis Owen-
dc.contributor.authorWard, Joey-
dc.contributor.authorGustafsson, Stefan-
dc.date.accessioned2017-05-25T06:27:35Z-
dc.date.available2017-05-25T06:27:35Z-
dc.date.issued2017-02-01-
dc.identifier.citationThe Lancet Diabetes and Endocrinology, 2017, vol. 5, no. 2, pp. 97-105en_US
dc.identifier.issn22138595-
dc.identifier.urihttps://hdl.handle.net/20.500.14279/10079-
dc.description.abstractStatin 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. Methods In 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. Findings Data were available for more than 550 000 individuals and 51 623 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 (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, −0·01 to 0·08), fasting insulin (0·00%, −0·06 to 0·07), and BMI (0·11 kg/m2, −0·09 to 0·30). Interpretation PCSK9 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. Funding British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.en_US
dc.formatpdfen_US
dc.language.isoenen_US
dc.relation.ispartofThe Lancet Diabetes and Endocrinologyen_US
dc.rights© The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license.en_US
dc.subjectHeart diseaseen_US
dc.subjectLDL cholesterolen_US
dc.subjectDiabetesen_US
dc.titlePCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation studyen_US
dc.typeArticleen_US
dc.collaborationUniversity College Londonen_US
dc.collaborationUniversity of Oxforden_US
dc.collaborationEmory Clinicen_US
dc.collaborationWellcome Trust Centre for Human Geneticsen_US
dc.collaborationUniversity of Glasgowen_US
dc.collaborationUniversidade Federal de Pelotasen_US
dc.collaborationUniversity of South Australiaen_US
dc.collaborationUCL Institute of Child Healthen_US
dc.collaborationICIN-Netherlands Heart Instituteen_US
dc.collaborationUniversity of Amsterdamen_US
dc.collaborationResearch Group On Geriatricsen_US
dc.collaborationCharité-Universitätsmedizin Berlinen_US
dc.collaborationUniversitat zu Lubecken_US
dc.collaborationMax Planck Instituteen_US
dc.collaborationMedizinische Universitat Innsbrucken_US
dc.collaborationBradford Royal Infirmaryen_US
dc.collaborationUniversity of Bristolen_US
dc.collaborationSt George's University of Londonen_US
dc.collaborationThe University of Edinburghen_US
dc.collaborationTyoterveyslaitosen_US
dc.collaborationCentre Hospitalier Universitaire Vaudoisen_US
dc.collaborationVascular Screening and Diagnostic Centreen_US
dc.collaborationCyprus University of Technologyen_US
dc.collaborationUniversity Medical Center Utrechten_US
dc.collaborationUniversita degli Studi di Torinoen_US
dc.collaborationHuman Genetics Foundationen_US
dc.collaborationUniversity of Cambridgeen_US
dc.collaborationInstitute of Internal and Preventive Medicineen_US
dc.collaborationCollegium Medicum Uniwersytet Jagiellonskiegoen_US
dc.collaborationNational Institute of Public Health Pragueen_US
dc.collaborationLithuanian University of Health Sciencesen_US
dc.collaborationResearch Centre for Prevention and Healthen_US
dc.collaborationKobenhavns Universiteten_US
dc.collaborationMarshfield Clinic Research Instituteen_US
dc.collaborationChildrens Hospital of Philadelphiaen_US
dc.collaborationGroup Health Cooperativeen_US
dc.collaborationEssentia Institute of Rural Healthen_US
dc.collaborationGeisinger Medical Centeren_US
dc.collaborationWashington Universityen_US
dc.collaborationMayo Clinicen_US
dc.collaborationDivision of Clinical Pharmacologyen_US
dc.collaborationVanderbilt Universityen_US
dc.collaborationFred Hutchinson Cancer Research Centeren_US
dc.collaborationNewcastle Universityen_US
dc.collaborationHunter Medical Research Instituteen_US
dc.collaborationPopulation Health Research Instituteen_US
dc.collaborationMcMaster Universityen_US
dc.collaborationUniversity of Groningenen_US
dc.collaborationLeiden University Medical Centeren_US
dc.collaborationUppsala Universiteten_US
dc.collaborationErasmus University Medical Centeren_US
dc.collaborationUniversity Medicine Greifswalden_US
dc.collaborationUniversitat Regensburgen_US
dc.collaborationDeutsches Zentrum fur Herz-Kreislauf-Forschung e. V.en_US
dc.collaborationLondon School of Hygiene and Tropical Medicineen_US
dc.collaborationUniversite Lille 2 Droit et Santeen_US
dc.collaborationGenomique Integrative et Modelisation des Maladies Metaboliquesen_US
dc.collaborationCentre for Epidemiology and Population Health (CESP)en_US
dc.collaborationCentre Hospitalier Universitaire de Nantesen_US
dc.collaborationUniversity of Essexen_US
dc.collaborationNuffield Department of Clinical Medicineen_US
dc.collaborationBrigham and Women's Hospitalen_US
dc.collaborationUniversity of North Carolina at Chapel Hill School of Medicineen_US
dc.collaborationGeisinger Health Systemen_US
dc.subject.categoryHealth Sciencesen_US
dc.journalsOpen Accessen_US
dc.countryUnited Kingdomen_US
dc.countryUnited Statesen_US
dc.countryBrazilen_US
dc.countryAustraliaen_US
dc.countryNetherlandsen_US
dc.countryGermanyen_US
dc.countryAustriaen_US
dc.countryFinlanden_US
dc.countrySwitzerlanden_US
dc.countryCyprusen_US
dc.countryItalyen_US
dc.countryRussiaen_US
dc.countryPolanden_US
dc.countryCzech Republicen_US
dc.countryLithuaniaen_US
dc.countryDenmarken_US
dc.countryCanadaen_US
dc.countrySwedenen_US
dc.countryFranceen_US
dc.subject.fieldMedical and Health Sciencesen_US
dc.publicationPeer Revieweden_US
dc.identifier.doi10.1016/S2213-8587(16)30396-5en_US
dc.relation.issue2en_US
dc.relation.volume5en_US
cut.common.academicyear2016-2017en_US
dc.identifier.spage97en_US
dc.identifier.epage105en_US
item.openairetypearticle-
item.cerifentitytypePublications-
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_6501-
item.languageiso639-1en-
crisitem.author.deptDepartment of Rehabilitation Sciences-
crisitem.author.facultyFaculty of Health Sciences-
crisitem.author.orcid0000-0002-6085-568X-
crisitem.author.parentorgFaculty of Health Sciences-
crisitem.journal.journalissn2213-8587-
crisitem.journal.publisherElsevier-
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