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description Publicationkeyboard_double_arrow_right Article , Other literature type 2018 Netherlands, Netherlands, Netherlands, United Kingdom, Italy, Netherlands, France, Croatia, Netherlands, Australia, Netherlands, Italy, United Kingdom, Italy, Netherlands, Italy, Netherlands, United KingdomPublisher:Elsevier BV Publicly fundedFunded by:EC | ePerMed, WTEC| ePerMed ,WTLigthart, Symen; Vaez, Ahmad; Võsa, Urmo; Stathopoulou, Maria G.; de Vries, Paul S.; Prins, Bram P.; Van der Most, Peter J.; Tanaka, Toshiko; Naderi, Elnaz; Rose, Lynda M.; Wu, Ying; Karlsson, Robert; Barbalic, Maja; Lin, Honghuang; Pool, René; Zhu, Gu; Macé, Aurélien; Sidore, Carlo; Trompet, Stella; Mangino, Massimo; Sabater-Lleal, Maria; Kemp, John P.; Abbasi, Ali; Kacprowski, Tim; Verweij, Niek; Smith, Albert V.; Huang, Tao; Marzi, Carola; Feitosa, Mary F.; Lohman, Kurt K.; Kleber, Marcus E.; Milaneschi, Yuri; Mueller, Christian; Huq, Mahmudul; Vlachopoulou, Efthymia; Lyytikäinen, Leo-Pekka; Oldmeadow, Christopher; Deelen, Joris; Perola, Markus; Zhao, Jing Hua; Feenstra, Bjarke; Amini, Marzyeh; Lahti, Jari; Schraut, Katharina E.; Fornage, Myriam; Suktitipat, Bhoom; Chen, Wei-Min; Li, Xiaohui; Nutile, Teresa; Malerba, Giovanni; Luan, Jian’an; Bak, Tom; Schork, Nicholas; Del Greco M., Fabiola; Thiering, Elisabeth; Mahajan, Anubha; Marioni, Riccardo E.; Mihailov, Evelin; Eriksson, Joel; Ozel, Ayse Bilge; Zhang, Weihua; Nethander, Maria; Cheng, Yu-Ching; Aslibekyan, Stella; Ang, Wei; Gandin, Ilaria; Yengo, Loïc; Portas, Laura; Kooperberg, Charles; Hofer, Edith; Rajan, Kumar B.; Schurmann, Claudia; den Hollander, Wouter; Ahluwalia, Tarunveer S.; Zhao, Jing; Draisma, Harmen H.M.; Ford, Ian; Timpson, Nicholas; Teumer, Alexander; Huang, Hongyan; Wahl, Simone; Liu, YongMei; Huang, Jie; Uh, Hae-Won; Geller, Frank; Joshi, Peter K.; Yanek, Lisa R.; Trabetti, Elisabetta; Lehne, Benjamin; Vozzi, Diego; Verbanck, Marie; Biino, Ginevra; Saba, Yasaman; Meulenbelt, Ingrid; O’Connell, Jeff R.; Laakso, Markku; Giulianini, Franco; Magnusson, Patrik K.E.; Ballantyne, Christie M.; Hottenga, Jouke Jan; Montgomery, Grant W.; Rivadineira, Fernando; Rueedi, Rico; Steri, Maristella; Herzig, Karl-Heinz; Stott, David J.; Menni, Cristina; Frånberg, Mattias; St. Pourcain, Beate; Felix, Stephan B.; Pers, Tune H.; Bakker, Stephan J.L.; Kraft, Peter; Peters, Annette; Vaidya, Dhananjay; Delgado, Graciela; Smit, Johannes H.; Großmann, Vera; Sinisalo, Juha; Seppälä, Ilkka; Williams, Stephen R.; Holliday, Elizabeth G.; Moed, Matthijs; Langenberg, Claudia; Räikkönen, Katri; Ding, Jingzhong; Campbell, Harry; Sale, Michele M.; Chen, Yii-Der I.; James, Alan L.; Ruggiero, Daniela; Soranzo, Nicole; Hartman, Catharina A.; Smith, Erin N.; Berenson, Gerald S.; Fuchsberger, Christian; Hernandez, Dena; Tiesler, Carla M.T.; Giedraitis, Vilmantas; Liewald, David; Fischer, Krista; Mellström, Dan; Larsson, Anders; Wang, Yunmei; Scott, William R.; Lorentzon, Matthias; Beilby, John; Ryan, Kathleen A.; Pennell, Craig E.; Vuckovic, Dragana; Balkau, Beverly; Concas, Maria Pina; Schmidt, Reinhold; Mendes de Leon, Carlos F.; Bottinger, Erwin P.; Kloppenburg, Margreet; Paternoster, Lavinia; Boehnke, Michael; Musk, A.W.; Willemsen, Gonneke; Evans, David M.; Madden, Pamela A.F.; Kähönen, Mika; Kutalik, Zoltán; Zoledziewska, Magdalena; Karhunen, Ville; Kritchevsky, Stephen B.; Sattar, Naveed; Lachance, Genevieve; Clarke, Robert; Harris, Tamara B.; Raitakari, Olli T.; Attia, John R.; van Heemst, Diana; Kajantie, Eero; Sorice, Rossella; Gambaro, Giovanni; Scott, Robert A.; Hicks, Andrew A.; Ferrucci, Luigi; Standl, Marie; Lindgren, Cecilia M.; Starr, John M.; Karlsson, Magnus; Lind, Lars; Li, Jun Z.; Chambers, John C.; Mori, Trevor A.; de Geus, Eco J.C.N.; Heath, Andrew C.; Martin, Nicholas G.; Auvinen, Juha; Buckley, Brendan M.; de Craen, Anton J.M.; Waldenberger, Melanie; Strauch, Konstantin; Meitinger, Thomas; Scott, Rodney J.; McEvoy, Mark; Beekman, Marian; Pedersen, Nancy L.; Cucca, Francesco; Jukema, J. Wouter; Zeller, Tanja; Uitterlinden, André G.; Gudnason, Vilmundur; Wild, Philipp S.; Melbye, Mads; Penninx, Brenda W.J.H.; Ciullo, Marina; Zaza, Gianluigi; Palmer, Lyle J.; Pramstaller, Peter P.; Bandinelli, Stefania; Heinrich, Joachim; Vandenput, Liesbeth; Ohlsson, Claes; Lehtimäki, Terho; Robino, Antonietta; Froguel, Philippe; Koenig, Wolfgang; Loos, Ruth J.F.; Smith, George Davey; Morris, Andrew P.; Visvikis-Siest, Sophie; Benjamin, Emelia J.; Jamshidi, Yalda; Abdollahi, Mohammadreza; van Duijn, Cornelia M.;handle: 1887/86903 , 11562/986920 , 21.11116/0000-000B-47C1-B , 1871.1/a6f9b3f3-837f-497b-a232-9276dc4e4e7c , 11370/faf23272-0ebb-4d5f-889f-35e7823ccafe , 1983/c7ea7935-1b05-4bd6-8ca0-eb7fc6e811cf , 1765/111671 , 11368/3005048 , 21.11116/0000-0002-7284-8 , 21.11116/0000-0002-7285-7 , 21.11116/0000-0002-7286-6 , 21.11116/0000-0002-7282-A
pmid: 30388399
pmc: PMC6218410
handle: 1887/86903 , 11562/986920 , 21.11116/0000-000B-47C1-B , 1871.1/a6f9b3f3-837f-497b-a232-9276dc4e4e7c , 11370/faf23272-0ebb-4d5f-889f-35e7823ccafe , 1983/c7ea7935-1b05-4bd6-8ca0-eb7fc6e811cf , 1765/111671 , 11368/3005048 , 21.11116/0000-0002-7284-8 , 21.11116/0000-0002-7285-7 , 21.11116/0000-0002-7286-6 , 21.11116/0000-0002-7282-A
pmid: 30388399
pmc: PMC6218410
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
CORE (RIOXX-UK Aggre... arrow_drop_down CORE (RIOXX-UK Aggregator)Article . 2018License: CC BY NC NDData sources: CORE (RIOXX-UK Aggregator)LUMC Scholarly Publications; NARCISOther literature type . Article . 2018NARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di VeronaThe American Journal of Human GeneticsArticleLicense: Elsevier Non-CommercialData sources: UnpayWallSpiral - Imperial College Digital RepositoryArticle . 2018Data sources: Spiral - Imperial College Digital RepositoryRecolector de Ciencia Abierta, RECOLECTAArticle . 2018Data sources: Recolector de Ciencia Abierta, RECOLECTAOxford University Research ArchiveOther literature type . 2018Data sources: Oxford University Research ArchiveCroatian Scientific Bibliography - CROSBIOther literature type . 2018Data sources: Croatian Scientific Bibliography - CROSBIThe American Journal of Human GeneticsOther literature type . Article . 2018 . Peer-reviewedLicense: Elsevier Non-CommercialNARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di Veronaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 301 citations 301 popularity Top 0.1% influence Top 10% impulse Top 0.1% Powered by BIP!visibility 52visibility views 52 download downloads 197 Powered bymore_vert CORE (RIOXX-UK Aggre... arrow_drop_down CORE (RIOXX-UK Aggregator)Article . 2018License: CC BY NC NDData sources: CORE (RIOXX-UK Aggregator)LUMC Scholarly Publications; NARCISOther literature type . Article . 2018NARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di VeronaThe American Journal of Human GeneticsArticleLicense: Elsevier Non-CommercialData sources: UnpayWallSpiral - Imperial College Digital RepositoryArticle . 2018Data sources: Spiral - Imperial College Digital RepositoryRecolector de Ciencia Abierta, RECOLECTAArticle . 2018Data sources: Recolector de Ciencia Abierta, RECOLECTAOxford University Research ArchiveOther literature type . 2018Data sources: Oxford University Research ArchiveCroatian Scientific Bibliography - CROSBIOther literature type . 2018Data sources: Croatian Scientific Bibliography - CROSBIThe American Journal of Human GeneticsOther literature type . Article . 2018 . Peer-reviewedLicense: Elsevier Non-CommercialNARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di Veronaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2013 Netherlands, United Kingdom, United KingdomPublisher:Elsevier BV Funded by:NWO | NCHA Subsidiebesluit 2008..., NIH | CHANGES IN HEALTH: SOCIO-..., AKA | Carotid Intima Media Thic... +7 projectsNWO| NCHA Subsidiebesluit 2008-2012 ,NIH| CHANGES IN HEALTH: SOCIO-ECONOMIC STATUS AND PATHWAYS ,AKA| Carotid Intima Media Thickness (IMT) and IMT-Progression as Predictors of Vascular Events in a High Risk European Population (IMPROVE) ,NWO| Sustainable ammonia synthesis powered by renewable electricity ,UKRI| Centre for molecular-based causal analyses in health and disease ,WT| Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics. ,NIH| Health behaviors over the adult lifecourse and cognitive aging ,NIH| SOCIAL AND OCCUPATIONAL INFLUENCES ON HEALTH AND ILLNESS ,EC| PHASE ,EC| FADMichael V. Holmes; Tabassome Simon; Holly J. Exeter; Lasse Folkersen; Folkert W. Asselbergs; Montse Guardiola; Jackie A. Cooper; Jutta Palmen; Jaroslav A. Hubacek; Kathryn F. Carruthers; Benjamin D. Horne; Kimberly D. Brunisholz; Jessica L. Mega; Erik P A Van Iperen; Mingyao Li; Maarten Leusink; Stella Trompet; Jeffrey J. W. Verschuren; G. Kees Hovingh; Abbas Dehghan; Christopher P. Nelson; Salma Kotti; Nicolas Danchin; Markus Scholz; Christiane L Haase; Dietrich Rothenbacher; Daniel I. Swerdlow; Karoline Kuchenbaecker; Eleonora Staines-Urias; Anuj Goel; Ferdinand Van 'T Hooft; Karl Gertow; Ulf de Faire; Andrie G. Panayiotou; Elena Tremoli; Damiano Baldassarre; Fabrizio Veglia; Lesca M. Holdt; Frank Beutner; Ron T. Gansevoort; Gerjan Navis; Irene Mateo Leach; Lutz P. Breitling; Hermann Brenner; Joachim Thiery; Dhayana Dallmeier; Anders Franco-Cereceda; Jolanda M. A. Boer; Jeffrey W. Stephens; Marten H. Hofker; Alain Tedgui; Albert Hofman; André G. Uitterlinden; Vera Adamkova; Jan Pitha; N. Charlotte Onland-Moret; Maarten J. Cramer; Hendrik M. Nathoe; Wilko Spiering; Olaf H. Klungel; Meena Kumari; Peter H. Whincup; David A. Morrow; Peter S. Braund; Alistair S. Hall; Anders G. Olsson; Pieter A. Doevendans; Mieke D. Trip; Martin D. Tobin; Anders Hamsten; Hugh Watkins; Wolfgang Koenig; Andrew N. Nicolaides; Daniel Teupser; Ian N.M. Day; John F. Carlquist; Tom R. Gaunt; Ian Ford; Naveed Sattar; Sotirios Tsimikas; Gregory G. Schwartz; Debbie A Lawlor; Richard W Morris; Manjinder S. Sandhu; Rudolf Poledne; Anke H. Maitland-van der Zee; Kay-Tee Khaw; Brendan J. Keating; Pim van der Harst; Jackie F. Price; Shamir R. Mehta; Salim Yusuf; Jaqueline C M Witteman; Oscar H. Franco; J. Wouter Jukema; Peter de Knijff; Anne Tybjærg-Hansen; Daniel J. Rader; Martin Farrall; Nilesh J. Samani; Mika Kivimäki; Keith A.A. Fox; Steve E. Humphries; Jeffrey L. Anderson; S. Matthijs Boekholdt; Tom Palmer; Per Eriksson; Guillaume Paré; Aroon D. Hingorani; Marc S. Sabatine; Ziad Mallat; Juan P. Casas; Philippa J. Talmud;Objectives:\ud This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.<p></p>\ud \ud Background:\ud Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy.<p></p>\ud \ud Methods:\ud We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable.<p></p>\ud \ud Results:\ud PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE.<p></p>\ud \ud Conclusions:\ud Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.<p></p>
CORE (RIOXX-UK Aggre... arrow_drop_down Journal of the American College of CardiologyArticle . 2013Full-Text: http://europepmc.org/articles/PMC3826105Data sources: PubMed CentralCORE (RIOXX-UK Aggregator)Article . 2013Full-Text: https://eprints.gla.ac.uk/88442/1/88442.pdfData sources: CORE (RIOXX-UK Aggregator)NARCIS; Journal of the American College of CardiologyArticle . 2013NARCIS; Journal of the American College of CardiologyArticle . 2013LUMC Scholarly Publications; Leiden University Scholarly Publications Repository; NARCISOther literature type . Article . 2013Journal of the American College of CardiologyArticle . 2013Data sources: Oxford University Research Archiveadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 130 citations 130 popularity Top 10% influence Top 10% impulse Top 1% Powered by BIP!download 96download downloads 96 Powered bymore_vert CORE (RIOXX-UK Aggre... arrow_drop_down Journal of the American College of CardiologyArticle . 2013Full-Text: http://europepmc.org/articles/PMC3826105Data sources: PubMed CentralCORE (RIOXX-UK Aggregator)Article . 2013Full-Text: https://eprints.gla.ac.uk/88442/1/88442.pdfData sources: CORE (RIOXX-UK Aggregator)NARCIS; Journal of the American College of CardiologyArticle . 2013NARCIS; Journal of the American College of CardiologyArticle . 2013LUMC Scholarly Publications; Leiden University Scholarly Publications Repository; NARCISOther literature type . Article . 2013Journal of the American College of CardiologyArticle . 2013Data sources: Oxford University Research Archiveadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type 2017Embargo end date: 16 Feb 2017 Sweden, France, United Kingdom, Poland, Italy, United Kingdom, Cyprus, United Kingdom, Italy, Netherlands, United Kingdom EnglishPublisher:Elsevier BV Funded by:EC | BIORISE, WTEC| BIORISE ,WTSchmidt, A.F.; Swerdlow, D.I.; Holmes, M.V.; Patel, R.S.; Fairhurst-Hunter, Z.; Lyall, D.M.; Hartwig, F.P.; Horta, B.L.; Hypponen, E.; Power, C.; Moldovan, M.; Iperen, E. van; Hovingh, G.K.; Demuth, I.; Norman, K.; Steinhagen-Thiessen, E.; Demuth, J.; Bertram, L.; Liu, T.; Coassin, S.; Willeit, J.; Kiechl, S.; Willeit, K.; Mason, D.; Wright, J.; Morris, R.; Wanamethee, G.; Whincup, P.; Ben-Shlomo, Y.; McLachlan, S.; Price, J.F.; Kivimaki, M.; Welch, C.; Sanchez-Galvez, A.; Marques-Vidal, P.; Nicolaides, A.; Panayiotou, A.G.; Onland-Moret, N.C.; Schouw, Y.T. van der; Matullo, G.; Fiorito, G.; Guarrera, S.; Sacerdote, C.; Wareham, N.J.; Langenberg, C.; Scott, R.; Luan, J.A.; Bobak, M.; Malyutina, S.A.; Pajak, A.; Kubinova, R.; Tamosiunas, A.; Pikhart, H.; Husemoen, L.L.N.; Grarup, N.; Pedersen, O.; Hansen, T.; Linneberg, A.; Simonsen, K.S.; Cooper, J.; Humphries, S.E.; Brilliant, M.; Kitchner, T.; Hakonarson, H.; Carrell, D.S.; McCarty, C.A.; Kirchner, H.L.; Larson, E.B.; Crosslin, D.R.; Andrade, M. de; Roden, D.M.; Denny, J.C.; Carty, C.; Hancock, S.; Attia, J.; Holliday, E.; Donnell, M.O.; Yusuf, S.; Chong, M.; Pare, G.; Harst, P. van der; Said, M.A.; Eppinga, R.N.; Verweij, N.; Snieder, H.; Christen, T.; Mook-Kanamori, D.O.; Gustafsson, S.; Lind, L.; Ingelsson, E.; Pazoki, R.; Franco, O.; Hofman, A.; Uitterlinden, A.; Dehghan, A.; Teumer, A.; Baumeister, S.; Dorr, M.; Lerch, M.M.; Volker, U.; Volzke, H.; Ward, J.; Pell, J.P.; Smith, D.J.; Meade, T.; Maitland-van der Zee, A.H.; Baranova, E.V.; Young, R.; Ford, I.; Campbell, A.; Padmanabhan, S.; Bots, M.L.; Grobbee, D.E.; Froguel, P.; Thuillier, D.; Balkau, B.; Bonnefond, A.; Cariou, B.; Smart, M.; Bao, Y.; Kumari, M.; Mahajan, A.; Ridker, P.M.; Chasman, D.I.; Reiner, A.P.; Lange, L.A.; Ritchie, M.D.; Asselbergs, F.W.; Casas, J.P.; Keating, B.J.; Preiss, D.; Hingorani, A.D.; Sattar, N.; LifeLines Cohort Study Grp; UCLEB Consortium;doi: 10.17863/cam.7909
handle: 1887/111905 , 1983/b842e1d8-febc-49c9-8b9b-a3f34a94e1df , 11388/245300 , 20.500.11820/87149176-4f45-435c-9bd4-e29ac44c05fb , 11858/00-001M-0000-002C-6322-4 , 11858/00-001M-0000-002C-6324-F , 2318/1635254 , 1983/f4884543-93c4-4037-a3a4-617beb72b74c
pmc: PMC5266795
BACKGROUND: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.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.
Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2017Full-Text: http://europepmc.org/articles/PMC5266795Data sources: PubMed CentralLUMC Scholarly Publications; NARCISOther literature type . Article . 2016Spiral - Imperial College Digital RepositoryArticle . 2016Data sources: Spiral - Imperial College Digital Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen 216 citations 216 popularity Top 1% influence Top 10% impulse Top 0.1% Powered by BIP!visibility 32visibility views 32 download downloads 390 Powered bymore_vert Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2017Full-Text: http://europepmc.org/articles/PMC5266795Data sources: PubMed CentralLUMC Scholarly Publications; NARCISOther literature type . Article . 2016Spiral - Imperial College Digital RepositoryArticle . 2016Data sources: Spiral - Imperial College Digital Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type , Preprint 2018 Poland, Italy, Italy, Switzerland, Cyprus, Lithuania, United Kingdom, United Kingdom, Denmark, United Kingdom, United Kingdom, United Kingdom, Netherlands, Australia, SwedenPublisher:Cold Spring Harbor Laboratory Funded by:NIH | Alzheimer's Disease Genet..., NIH | ALZHEIMERS DISEASE DATA C..., WT | Determinants of cardiovas... +10 projectsNIH| Alzheimer's Disease Genetics Consortium ,NIH| ALZHEIMERS DISEASE DATA COORDINATING CENTER ,WT| Determinants of cardiovascular diseases in Eastern Europe: a multi-centre cohort study. ,NIH| National Cell Repository for Alzheimer's Disease (NCRAD) ,NIH| AGES STUDY-THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENNIUM-260012100 ,UKRI| Centre for Health service and Academic Partnership in Translational eHealth Research (CHAPTER) ,EC| BIORISE ,NIH| Alzheimer's Disease Genetics Consortium ,WT| A Powerful, Genome-Wide Association Scan for Susceptibility Genes for late-onset Alzheimer's disease ,WT| Determinants of cardiovascular diseases in Eastern Europe: Longitudinal follow up of a multi-centre cohort study (The HAPIEE Project). ,NIH| Collaborative GWAS of Dementia, AD and related MRI and Cognitive Endophenotypes ,NIH| CHARGE consortium: gene discovery for CVD and aging phenotypes ,NIH| Health disparities and aging in societies in transitionAmand F. Schmidt; Michael V. Holmes; David Preiss; Daniel I. Swerdlow; Spiros Denaxas; Ghazaleh Fatemifar; Rupert Faraway; Chris Finan; Dennis Valentine; Zammy Fairhurst-Hunter; Fernando Pires Hartwig; Bernardo L. Horta; Elina Hyppönen; Christine Power; Max Moldovan; Erik P A Van Iperen; Kees Hovingh; Ilja Demuth; Kristina Norman; Elisabeth Steinhagen-Thiessen; Juri Demuth; Lars Bertram; Christina M. Lill; Stefan Coassin; Johann Willeit; Stefan Kiechl; Karin Willeit; Dan Mason; John Wright; Richard W Morris; Goya Wanamethee; Peter H. Whincup; Yoav Ben-Shlomo; Stela McLachlan; Jackie F. Price; Mika Kivimäki; Catherine Welch; Adelaida Sanchez-Galvez; Pedro Marques-Vidal; Andrew N. Nicolaides; Andrie G. Panayiotou; N. Charlotte Onland-Moret; Yvonne T. van der Schouw; Giuseppe Matullo; Giovanni Fiorito; Simonetta Guarrera; Carlotta Sacerdote; Nicholas J. Wareham; Claudia Langenberg; Robert A. Scott; Jian'an Luan; Martin Bobak; Sofia Malyutina; Andrzej Pajak; Ruzena Kubinova; Abdonas Tamosiunas; Hynek Pikhart; Niels Grarup; Oluf Pedersen; Torben Hansen; Allan Linneberg; Tine Jess; Jackie A. Cooper; Steve E. Humphries; Murray H. Brilliant; Terrie Kitchner; Hakon Hakonarson; David Carrell; Catherine A. McCarty; Kirchner H. Lester; Eric B. Larson; David R. Crosslin; Mariza de Andrade; Dan M. Roden; Joshua C. Denny; Cara L. Carty; Stephen Hancock; John Attia; Elizabeth G. Holliday; Rodney J. Scott; Peter W. Schofield; Martin O'Donnell; Salim Yusuf; Michael Chong; Guillaume Paré; Pim van der Harst; M. Abdullah Said; Ruben N. Eppinga; Niek Verweij; Harold Snieder; Tim Christen; Dennis O. Mook-Kanamori; Stefan Gustafsson; Lars Lind; Erik Ingelsson; Raha Pazoki; Oscar H. Franco; Albert Hofman; André G. Uitterlinden; Abbas Dehghan; Alexander Teumer; Sebastian E. Baumeister; Marcus Dörr; Markus M. Lerch; Uwe Völker; Henry Völzke; Joey Ward; Jill P. Pell; Tom W. Meade; Ingrid E. Christophersen; Anke H. Maitland-van der Zee; Ekaterina V. Baranova; Robin Young; Ian Ford; Archie Campbell; Sandosh Padmanabhan; Michiel L. Bots; Diederick E. Grobbee; Philippe Froguel; Dorothée Thuillier; Ronan Roussel; Amélie Bonnefond; Bertrand Cariou; Melissa C. Smart; Yanchun Bao; Meena Kumari; Anubha Mahajan; Jemma C. Hopewell; Sudha Seshadri; Caroline Dale; Rui Bebiano Da Providencia E Costa; Paul M. Ridker; Daniel I. Chasman; Alexander P. Reiner; Marylyn D. Ritchie; Leslie A. Lange; Alex J. Cornish; Sara E. Dobbins; Kari Hemminki; Ben Kinnersley; Marc Sanson; Karim Labreche; Matthias Simon; Melissa L. Bondy; Philip J. Law; Helen E. Speedy; James M. Allan; Ni Li; Molly Went; Niels Weinhold; Gareth J. Morgan; Pieter Sonneveld; Björn Nilsson; Hartmut Goldschmidt; Amit Sud; Andreas Engert; Markus Hansson; Harry Hemingway; Folkert W. Asselbergs; Riyaz S. Patel; Brendan J. Keating; Naveed Sattar; Richard S. Houlston; Juan P. Casas; Aroon D. Hingorani;doi: 10.1101/329052 , 10.1186/s12872-019-1187-z , 10.17863/cam.59255 , 10.17863/cam.43205 , 10.7892/boris.137329
pmc: PMC6820948
pmid: 31664920
doi: 10.1101/329052 , 10.1186/s12872-019-1187-z , 10.17863/cam.59255 , 10.17863/cam.43205 , 10.7892/boris.137329
pmc: PMC6820948
pmid: 31664920
AbstractBackgroundWe characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.MethodsPublished and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Fourteen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentrationResultsThe PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95%CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95%CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95%CI 0.57; 1.22) for the GS, compared to 0.85 (95%CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95%CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable.ConclusionsGenetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. Apparent discordance between genetic associations and trial outcome for T2DM might be explained lack by a of statistical precision, or differences in the nature and duration of genetic versus pharmacological perturbation of PCSK9.FundingThis research was funded by the British Heart Foundation (SP/13/6/30554, RG/10/12/28456, FS/18/23/33512), UCL Hospitals NIHR Biomedical Research Centre, by the Rosetrees and Stoneygate Trusts.Condensed abstractEvidence on the long-term efficacy and safety of therapeutic inhibition of PCSK9 is lacking. To explore potential long-term effects of PCSK9 inhibition, we characterised the phenotypic consequence of LDL-cholesterol lowering variants at the PCSK9 locus. A PCSK9 gene score comprising 4 SNPs recapitulated the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and risk of myocardial infarction, and was associated with an increased risk of type 2 diabetes. No associations with safety outcomes such as cancer, COPD, Alzheimer’s disease or atrial fibrillation were identified. Our findings suggest PCSK9 inhibition may be safe and effective during prolonged use.
Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2019Full-Text: http://europepmc.org/articles/PMC6820948Data sources: PubMed CentralOxford University Research Archive; BMC Cardiovascular Disorders; UnissResearchOther literature type . Article . 2019 . Peer-reviewedLicense: CC BYNARCIS; BMC Cardiovascular DisordersArticle . 2019bioRxivPreprint . 2018Spiral - Imperial College Digital RepositoryArticle . 2019Data sources: Spiral - Imperial College Digital RepositoryCopenhagen University Research Information SystemArticle . 2019Data sources: Copenhagen University Research Information SystemLUMC Scholarly Publications; NARCISOther literature type . Article . 2019UniSA Research Outputs RepositoryArticle . 2019 . Peer-reviewedData sources: UniSA Research Outputs Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 30 citations 30 popularity Top 10% influence Average impulse Top 10% Powered by BIP!visibility 11visibility views 11 download downloads 26 Powered bymore_vert Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2019Full-Text: http://europepmc.org/articles/PMC6820948Data sources: PubMed CentralOxford University Research Archive; BMC Cardiovascular Disorders; UnissResearchOther literature type . Article . 2019 . Peer-reviewedLicense: CC BYNARCIS; BMC Cardiovascular DisordersArticle . 2019bioRxivPreprint . 2018Spiral - Imperial College Digital RepositoryArticle . 2019Data sources: Spiral - Imperial College Digital RepositoryCopenhagen University Research Information SystemArticle . 2019Data sources: Copenhagen University Research Information SystemLUMC Scholarly Publications; NARCISOther literature type . Article . 2019UniSA Research Outputs RepositoryArticle . 2019 . Peer-reviewedData sources: UniSA Research Outputs Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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description Publicationkeyboard_double_arrow_right Article , Other literature type 2018 Netherlands, Netherlands, Netherlands, United Kingdom, Italy, Netherlands, France, Croatia, Netherlands, Australia, Netherlands, Italy, United Kingdom, Italy, Netherlands, Italy, Netherlands, United KingdomPublisher:Elsevier BV Publicly fundedFunded by:EC | ePerMed, WTEC| ePerMed ,WTLigthart, Symen; Vaez, Ahmad; Võsa, Urmo; Stathopoulou, Maria G.; de Vries, Paul S.; Prins, Bram P.; Van der Most, Peter J.; Tanaka, Toshiko; Naderi, Elnaz; Rose, Lynda M.; Wu, Ying; Karlsson, Robert; Barbalic, Maja; Lin, Honghuang; Pool, René; Zhu, Gu; Macé, Aurélien; Sidore, Carlo; Trompet, Stella; Mangino, Massimo; Sabater-Lleal, Maria; Kemp, John P.; Abbasi, Ali; Kacprowski, Tim; Verweij, Niek; Smith, Albert V.; Huang, Tao; Marzi, Carola; Feitosa, Mary F.; Lohman, Kurt K.; Kleber, Marcus E.; Milaneschi, Yuri; Mueller, Christian; Huq, Mahmudul; Vlachopoulou, Efthymia; Lyytikäinen, Leo-Pekka; Oldmeadow, Christopher; Deelen, Joris; Perola, Markus; Zhao, Jing Hua; Feenstra, Bjarke; Amini, Marzyeh; Lahti, Jari; Schraut, Katharina E.; Fornage, Myriam; Suktitipat, Bhoom; Chen, Wei-Min; Li, Xiaohui; Nutile, Teresa; Malerba, Giovanni; Luan, Jian’an; Bak, Tom; Schork, Nicholas; Del Greco M., Fabiola; Thiering, Elisabeth; Mahajan, Anubha; Marioni, Riccardo E.; Mihailov, Evelin; Eriksson, Joel; Ozel, Ayse Bilge; Zhang, Weihua; Nethander, Maria; Cheng, Yu-Ching; Aslibekyan, Stella; Ang, Wei; Gandin, Ilaria; Yengo, Loïc; Portas, Laura; Kooperberg, Charles; Hofer, Edith; Rajan, Kumar B.; Schurmann, Claudia; den Hollander, Wouter; Ahluwalia, Tarunveer S.; Zhao, Jing; Draisma, Harmen H.M.; Ford, Ian; Timpson, Nicholas; Teumer, Alexander; Huang, Hongyan; Wahl, Simone; Liu, YongMei; Huang, Jie; Uh, Hae-Won; Geller, Frank; Joshi, Peter K.; Yanek, Lisa R.; Trabetti, Elisabetta; Lehne, Benjamin; Vozzi, Diego; Verbanck, Marie; Biino, Ginevra; Saba, Yasaman; Meulenbelt, Ingrid; O’Connell, Jeff R.; Laakso, Markku; Giulianini, Franco; Magnusson, Patrik K.E.; Ballantyne, Christie M.; Hottenga, Jouke Jan; Montgomery, Grant W.; Rivadineira, Fernando; Rueedi, Rico; Steri, Maristella; Herzig, Karl-Heinz; Stott, David J.; Menni, Cristina; Frånberg, Mattias; St. Pourcain, Beate; Felix, Stephan B.; Pers, Tune H.; Bakker, Stephan J.L.; Kraft, Peter; Peters, Annette; Vaidya, Dhananjay; Delgado, Graciela; Smit, Johannes H.; Großmann, Vera; Sinisalo, Juha; Seppälä, Ilkka; Williams, Stephen R.; Holliday, Elizabeth G.; Moed, Matthijs; Langenberg, Claudia; Räikkönen, Katri; Ding, Jingzhong; Campbell, Harry; Sale, Michele M.; Chen, Yii-Der I.; James, Alan L.; Ruggiero, Daniela; Soranzo, Nicole; Hartman, Catharina A.; Smith, Erin N.; Berenson, Gerald S.; Fuchsberger, Christian; Hernandez, Dena; Tiesler, Carla M.T.; Giedraitis, Vilmantas; Liewald, David; Fischer, Krista; Mellström, Dan; Larsson, Anders; Wang, Yunmei; Scott, William R.; Lorentzon, Matthias; Beilby, John; Ryan, Kathleen A.; Pennell, Craig E.; Vuckovic, Dragana; Balkau, Beverly; Concas, Maria Pina; Schmidt, Reinhold; Mendes de Leon, Carlos F.; Bottinger, Erwin P.; Kloppenburg, Margreet; Paternoster, Lavinia; Boehnke, Michael; Musk, A.W.; Willemsen, Gonneke; Evans, David M.; Madden, Pamela A.F.; Kähönen, Mika; Kutalik, Zoltán; Zoledziewska, Magdalena; Karhunen, Ville; Kritchevsky, Stephen B.; Sattar, Naveed; Lachance, Genevieve; Clarke, Robert; Harris, Tamara B.; Raitakari, Olli T.; Attia, John R.; van Heemst, Diana; Kajantie, Eero; Sorice, Rossella; Gambaro, Giovanni; Scott, Robert A.; Hicks, Andrew A.; Ferrucci, Luigi; Standl, Marie; Lindgren, Cecilia M.; Starr, John M.; Karlsson, Magnus; Lind, Lars; Li, Jun Z.; Chambers, John C.; Mori, Trevor A.; de Geus, Eco J.C.N.; Heath, Andrew C.; Martin, Nicholas G.; Auvinen, Juha; Buckley, Brendan M.; de Craen, Anton J.M.; Waldenberger, Melanie; Strauch, Konstantin; Meitinger, Thomas; Scott, Rodney J.; McEvoy, Mark; Beekman, Marian; Pedersen, Nancy L.; Cucca, Francesco; Jukema, J. Wouter; Zeller, Tanja; Uitterlinden, André G.; Gudnason, Vilmundur; Wild, Philipp S.; Melbye, Mads; Penninx, Brenda W.J.H.; Ciullo, Marina; Zaza, Gianluigi; Palmer, Lyle J.; Pramstaller, Peter P.; Bandinelli, Stefania; Heinrich, Joachim; Vandenput, Liesbeth; Ohlsson, Claes; Lehtimäki, Terho; Robino, Antonietta; Froguel, Philippe; Koenig, Wolfgang; Loos, Ruth J.F.; Smith, George Davey; Morris, Andrew P.; Visvikis-Siest, Sophie; Benjamin, Emelia J.; Jamshidi, Yalda; Abdollahi, Mohammadreza; van Duijn, Cornelia M.;handle: 1887/86903 , 11562/986920 , 21.11116/0000-000B-47C1-B , 1871.1/a6f9b3f3-837f-497b-a232-9276dc4e4e7c , 11370/faf23272-0ebb-4d5f-889f-35e7823ccafe , 1983/c7ea7935-1b05-4bd6-8ca0-eb7fc6e811cf , 1765/111671 , 11368/3005048 , 21.11116/0000-0002-7284-8 , 21.11116/0000-0002-7285-7 , 21.11116/0000-0002-7286-6 , 21.11116/0000-0002-7282-A
pmid: 30388399
pmc: PMC6218410
handle: 1887/86903 , 11562/986920 , 21.11116/0000-000B-47C1-B , 1871.1/a6f9b3f3-837f-497b-a232-9276dc4e4e7c , 11370/faf23272-0ebb-4d5f-889f-35e7823ccafe , 1983/c7ea7935-1b05-4bd6-8ca0-eb7fc6e811cf , 1765/111671 , 11368/3005048 , 21.11116/0000-0002-7284-8 , 21.11116/0000-0002-7285-7 , 21.11116/0000-0002-7286-6 , 21.11116/0000-0002-7282-A
pmid: 30388399
pmc: PMC6218410
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
CORE (RIOXX-UK Aggre... arrow_drop_down CORE (RIOXX-UK Aggregator)Article . 2018License: CC BY NC NDData sources: CORE (RIOXX-UK Aggregator)LUMC Scholarly Publications; NARCISOther literature type . Article . 2018NARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di VeronaThe American Journal of Human GeneticsArticleLicense: Elsevier Non-CommercialData sources: UnpayWallSpiral - Imperial College Digital RepositoryArticle . 2018Data sources: Spiral - Imperial College Digital RepositoryRecolector de Ciencia Abierta, RECOLECTAArticle . 2018Data sources: Recolector de Ciencia Abierta, RECOLECTAOxford University Research ArchiveOther literature type . 2018Data sources: Oxford University Research ArchiveCroatian Scientific Bibliography - CROSBIOther literature type . 2018Data sources: Croatian Scientific Bibliography - CROSBIThe American Journal of Human GeneticsOther literature type . Article . 2018 . Peer-reviewedLicense: Elsevier Non-CommercialNARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di Veronaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 301 citations 301 popularity Top 0.1% influence Top 10% impulse Top 0.1% Powered by BIP!visibility 52visibility views 52 download downloads 197 Powered bymore_vert CORE (RIOXX-UK Aggre... arrow_drop_down CORE (RIOXX-UK Aggregator)Article . 2018License: CC BY NC NDData sources: CORE (RIOXX-UK Aggregator)LUMC Scholarly Publications; NARCISOther literature type . Article . 2018NARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di VeronaThe American Journal of Human GeneticsArticleLicense: Elsevier Non-CommercialData sources: UnpayWallSpiral - Imperial College Digital RepositoryArticle . 2018Data sources: Spiral - Imperial College Digital RepositoryRecolector de Ciencia Abierta, RECOLECTAArticle . 2018Data sources: Recolector de Ciencia Abierta, RECOLECTAOxford University Research ArchiveOther literature type . 2018Data sources: Oxford University Research ArchiveCroatian Scientific Bibliography - CROSBIOther literature type . 2018Data sources: Croatian Scientific Bibliography - CROSBIThe American Journal of Human GeneticsOther literature type . Article . 2018 . Peer-reviewedLicense: Elsevier Non-CommercialNARCIS; The American Journal of Human GeneticsArticle . 2018IRIS - Università degli Studi di VeronaArticle . 2018Data sources: IRIS - Università degli Studi di Veronaadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article 2013 Netherlands, United Kingdom, United KingdomPublisher:Elsevier BV Funded by:NWO | NCHA Subsidiebesluit 2008..., NIH | CHANGES IN HEALTH: SOCIO-..., AKA | Carotid Intima Media Thic... +7 projectsNWO| NCHA Subsidiebesluit 2008-2012 ,NIH| CHANGES IN HEALTH: SOCIO-ECONOMIC STATUS AND PATHWAYS ,AKA| Carotid Intima Media Thickness (IMT) and IMT-Progression as Predictors of Vascular Events in a High Risk European Population (IMPROVE) ,NWO| Sustainable ammonia synthesis powered by renewable electricity ,UKRI| Centre for molecular-based causal analyses in health and disease ,WT| Understanding the genetic basis of common human diseases: core funding for the Wellcome Trust Centre for Human Genetics. ,NIH| Health behaviors over the adult lifecourse and cognitive aging ,NIH| SOCIAL AND OCCUPATIONAL INFLUENCES ON HEALTH AND ILLNESS ,EC| PHASE ,EC| FADMichael V. Holmes; Tabassome Simon; Holly J. Exeter; Lasse Folkersen; Folkert W. Asselbergs; Montse Guardiola; Jackie A. Cooper; Jutta Palmen; Jaroslav A. Hubacek; Kathryn F. Carruthers; Benjamin D. Horne; Kimberly D. Brunisholz; Jessica L. Mega; Erik P A Van Iperen; Mingyao Li; Maarten Leusink; Stella Trompet; Jeffrey J. W. Verschuren; G. Kees Hovingh; Abbas Dehghan; Christopher P. Nelson; Salma Kotti; Nicolas Danchin; Markus Scholz; Christiane L Haase; Dietrich Rothenbacher; Daniel I. Swerdlow; Karoline Kuchenbaecker; Eleonora Staines-Urias; Anuj Goel; Ferdinand Van 'T Hooft; Karl Gertow; Ulf de Faire; Andrie G. Panayiotou; Elena Tremoli; Damiano Baldassarre; Fabrizio Veglia; Lesca M. Holdt; Frank Beutner; Ron T. Gansevoort; Gerjan Navis; Irene Mateo Leach; Lutz P. Breitling; Hermann Brenner; Joachim Thiery; Dhayana Dallmeier; Anders Franco-Cereceda; Jolanda M. A. Boer; Jeffrey W. Stephens; Marten H. Hofker; Alain Tedgui; Albert Hofman; André G. Uitterlinden; Vera Adamkova; Jan Pitha; N. Charlotte Onland-Moret; Maarten J. Cramer; Hendrik M. Nathoe; Wilko Spiering; Olaf H. Klungel; Meena Kumari; Peter H. Whincup; David A. Morrow; Peter S. Braund; Alistair S. Hall; Anders G. Olsson; Pieter A. Doevendans; Mieke D. Trip; Martin D. Tobin; Anders Hamsten; Hugh Watkins; Wolfgang Koenig; Andrew N. Nicolaides; Daniel Teupser; Ian N.M. Day; John F. Carlquist; Tom R. Gaunt; Ian Ford; Naveed Sattar; Sotirios Tsimikas; Gregory G. Schwartz; Debbie A Lawlor; Richard W Morris; Manjinder S. Sandhu; Rudolf Poledne; Anke H. Maitland-van der Zee; Kay-Tee Khaw; Brendan J. Keating; Pim van der Harst; Jackie F. Price; Shamir R. Mehta; Salim Yusuf; Jaqueline C M Witteman; Oscar H. Franco; J. Wouter Jukema; Peter de Knijff; Anne Tybjærg-Hansen; Daniel J. Rader; Martin Farrall; Nilesh J. Samani; Mika Kivimäki; Keith A.A. Fox; Steve E. Humphries; Jeffrey L. Anderson; S. Matthijs Boekholdt; Tom Palmer; Per Eriksson; Guillaume Paré; Aroon D. Hingorani; Marc S. Sabatine; Ziad Mallat; Juan P. Casas; Philippa J. Talmud;Objectives:\ud This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.<p></p>\ud \ud Background:\ud Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy.<p></p>\ud \ud Methods:\ud We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable.<p></p>\ud \ud Results:\ud PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE.<p></p>\ud \ud Conclusions:\ud Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.<p></p>
CORE (RIOXX-UK Aggre... arrow_drop_down Journal of the American College of CardiologyArticle . 2013Full-Text: http://europepmc.org/articles/PMC3826105Data sources: PubMed CentralCORE (RIOXX-UK Aggregator)Article . 2013Full-Text: https://eprints.gla.ac.uk/88442/1/88442.pdfData sources: CORE (RIOXX-UK Aggregator)NARCIS; Journal of the American College of CardiologyArticle . 2013NARCIS; Journal of the American College of CardiologyArticle . 2013LUMC Scholarly Publications; Leiden University Scholarly Publications Repository; NARCISOther literature type . Article . 2013Journal of the American College of CardiologyArticle . 2013Data sources: Oxford University Research Archiveadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen hybrid 130 citations 130 popularity Top 10% influence Top 10% impulse Top 1% Powered by BIP!download 96download downloads 96 Powered bymore_vert CORE (RIOXX-UK Aggre... arrow_drop_down Journal of the American College of CardiologyArticle . 2013Full-Text: http://europepmc.org/articles/PMC3826105Data sources: PubMed CentralCORE (RIOXX-UK Aggregator)Article . 2013Full-Text: https://eprints.gla.ac.uk/88442/1/88442.pdfData sources: CORE (RIOXX-UK Aggregator)NARCIS; Journal of the American College of CardiologyArticle . 2013NARCIS; Journal of the American College of CardiologyArticle . 2013LUMC Scholarly Publications; Leiden University Scholarly Publications Repository; NARCISOther literature type . Article . 2013Journal of the American College of CardiologyArticle . 2013Data sources: Oxford University Research Archiveadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type 2017Embargo end date: 16 Feb 2017 Sweden, France, United Kingdom, Poland, Italy, United Kingdom, Cyprus, United Kingdom, Italy, Netherlands, United Kingdom EnglishPublisher:Elsevier BV Funded by:EC | BIORISE, WTEC| BIORISE ,WTSchmidt, A.F.; Swerdlow, D.I.; Holmes, M.V.; Patel, R.S.; Fairhurst-Hunter, Z.; Lyall, D.M.; Hartwig, F.P.; Horta, B.L.; Hypponen, E.; Power, C.; Moldovan, M.; Iperen, E. van; Hovingh, G.K.; Demuth, I.; Norman, K.; Steinhagen-Thiessen, E.; Demuth, J.; Bertram, L.; Liu, T.; Coassin, S.; Willeit, J.; Kiechl, S.; Willeit, K.; Mason, D.; Wright, J.; Morris, R.; Wanamethee, G.; Whincup, P.; Ben-Shlomo, Y.; McLachlan, S.; Price, J.F.; Kivimaki, M.; Welch, C.; Sanchez-Galvez, A.; Marques-Vidal, P.; Nicolaides, A.; Panayiotou, A.G.; Onland-Moret, N.C.; Schouw, Y.T. van der; Matullo, G.; Fiorito, G.; Guarrera, S.; Sacerdote, C.; Wareham, N.J.; Langenberg, C.; Scott, R.; Luan, J.A.; Bobak, M.; Malyutina, S.A.; Pajak, A.; Kubinova, R.; Tamosiunas, A.; Pikhart, H.; Husemoen, L.L.N.; Grarup, N.; Pedersen, O.; Hansen, T.; Linneberg, A.; Simonsen, K.S.; Cooper, J.; Humphries, S.E.; Brilliant, M.; Kitchner, T.; Hakonarson, H.; Carrell, D.S.; McCarty, C.A.; Kirchner, H.L.; Larson, E.B.; Crosslin, D.R.; Andrade, M. de; Roden, D.M.; Denny, J.C.; Carty, C.; Hancock, S.; Attia, J.; Holliday, E.; Donnell, M.O.; Yusuf, S.; Chong, M.; Pare, G.; Harst, P. van der; Said, M.A.; Eppinga, R.N.; Verweij, N.; Snieder, H.; Christen, T.; Mook-Kanamori, D.O.; Gustafsson, S.; Lind, L.; Ingelsson, E.; Pazoki, R.; Franco, O.; Hofman, A.; Uitterlinden, A.; Dehghan, A.; Teumer, A.; Baumeister, S.; Dorr, M.; Lerch, M.M.; Volker, U.; Volzke, H.; Ward, J.; Pell, J.P.; Smith, D.J.; Meade, T.; Maitland-van der Zee, A.H.; Baranova, E.V.; Young, R.; Ford, I.; Campbell, A.; Padmanabhan, S.; Bots, M.L.; Grobbee, D.E.; Froguel, P.; Thuillier, D.; Balkau, B.; Bonnefond, A.; Cariou, B.; Smart, M.; Bao, Y.; Kumari, M.; Mahajan, A.; Ridker, P.M.; Chasman, D.I.; Reiner, A.P.; Lange, L.A.; Ritchie, M.D.; Asselbergs, F.W.; Casas, J.P.; Keating, B.J.; Preiss, D.; Hingorani, A.D.; Sattar, N.; LifeLines Cohort Study Grp; UCLEB Consortium;doi: 10.17863/cam.7909
handle: 1887/111905 , 1983/b842e1d8-febc-49c9-8b9b-a3f34a94e1df , 11388/245300 , 20.500.11820/87149176-4f45-435c-9bd4-e29ac44c05fb , 11858/00-001M-0000-002C-6322-4 , 11858/00-001M-0000-002C-6324-F , 2318/1635254 , 1983/f4884543-93c4-4037-a3a4-617beb72b74c
pmc: PMC5266795
BACKGROUND: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.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.
Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2017Full-Text: http://europepmc.org/articles/PMC5266795Data sources: PubMed CentralLUMC Scholarly Publications; NARCISOther literature type . Article . 2016Spiral - Imperial College Digital RepositoryArticle . 2016Data sources: Spiral - Imperial College Digital Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen 216 citations 216 popularity Top 1% influence Top 10% impulse Top 0.1% Powered by BIP!visibility 32visibility views 32 download downloads 390 Powered bymore_vert Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2017Full-Text: http://europepmc.org/articles/PMC5266795Data sources: PubMed CentralLUMC Scholarly Publications; NARCISOther literature type . Article . 2016Spiral - Imperial College Digital RepositoryArticle . 2016Data sources: Spiral - Imperial College Digital Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.eudescription Publicationkeyboard_double_arrow_right Article , Other literature type , Preprint 2018 Poland, Italy, Italy, Switzerland, Cyprus, Lithuania, United Kingdom, United Kingdom, Denmark, United Kingdom, United Kingdom, United Kingdom, Netherlands, Australia, SwedenPublisher:Cold Spring Harbor Laboratory Funded by:NIH | Alzheimer's Disease Genet..., NIH | ALZHEIMERS DISEASE DATA C..., WT | Determinants of cardiovas... +10 projectsNIH| Alzheimer's Disease Genetics Consortium ,NIH| ALZHEIMERS DISEASE DATA COORDINATING CENTER ,WT| Determinants of cardiovascular diseases in Eastern Europe: a multi-centre cohort study. ,NIH| National Cell Repository for Alzheimer's Disease (NCRAD) ,NIH| AGES STUDY-THE REYKJAVIK STUDY OF HEALTHY AGING FOR THE NEW MILLENNIUM-260012100 ,UKRI| Centre for Health service and Academic Partnership in Translational eHealth Research (CHAPTER) ,EC| BIORISE ,NIH| Alzheimer's Disease Genetics Consortium ,WT| A Powerful, Genome-Wide Association Scan for Susceptibility Genes for late-onset Alzheimer's disease ,WT| Determinants of cardiovascular diseases in Eastern Europe: Longitudinal follow up of a multi-centre cohort study (The HAPIEE Project). ,NIH| Collaborative GWAS of Dementia, AD and related MRI and Cognitive Endophenotypes ,NIH| CHARGE consortium: gene discovery for CVD and aging phenotypes ,NIH| Health disparities and aging in societies in transitionAmand F. Schmidt; Michael V. Holmes; David Preiss; Daniel I. Swerdlow; Spiros Denaxas; Ghazaleh Fatemifar; Rupert Faraway; Chris Finan; Dennis Valentine; Zammy Fairhurst-Hunter; Fernando Pires Hartwig; Bernardo L. Horta; Elina Hyppönen; Christine Power; Max Moldovan; Erik P A Van Iperen; Kees Hovingh; Ilja Demuth; Kristina Norman; Elisabeth Steinhagen-Thiessen; Juri Demuth; Lars Bertram; Christina M. Lill; Stefan Coassin; Johann Willeit; Stefan Kiechl; Karin Willeit; Dan Mason; John Wright; Richard W Morris; Goya Wanamethee; Peter H. Whincup; Yoav Ben-Shlomo; Stela McLachlan; Jackie F. Price; Mika Kivimäki; Catherine Welch; Adelaida Sanchez-Galvez; Pedro Marques-Vidal; Andrew N. Nicolaides; Andrie G. Panayiotou; N. Charlotte Onland-Moret; Yvonne T. van der Schouw; Giuseppe Matullo; Giovanni Fiorito; Simonetta Guarrera; Carlotta Sacerdote; Nicholas J. Wareham; Claudia Langenberg; Robert A. Scott; Jian'an Luan; Martin Bobak; Sofia Malyutina; Andrzej Pajak; Ruzena Kubinova; Abdonas Tamosiunas; Hynek Pikhart; Niels Grarup; Oluf Pedersen; Torben Hansen; Allan Linneberg; Tine Jess; Jackie A. Cooper; Steve E. Humphries; Murray H. Brilliant; Terrie Kitchner; Hakon Hakonarson; David Carrell; Catherine A. McCarty; Kirchner H. Lester; Eric B. Larson; David R. Crosslin; Mariza de Andrade; Dan M. Roden; Joshua C. Denny; Cara L. Carty; Stephen Hancock; John Attia; Elizabeth G. Holliday; Rodney J. Scott; Peter W. Schofield; Martin O'Donnell; Salim Yusuf; Michael Chong; Guillaume Paré; Pim van der Harst; M. Abdullah Said; Ruben N. Eppinga; Niek Verweij; Harold Snieder; Tim Christen; Dennis O. Mook-Kanamori; Stefan Gustafsson; Lars Lind; Erik Ingelsson; Raha Pazoki; Oscar H. Franco; Albert Hofman; André G. Uitterlinden; Abbas Dehghan; Alexander Teumer; Sebastian E. Baumeister; Marcus Dörr; Markus M. Lerch; Uwe Völker; Henry Völzke; Joey Ward; Jill P. Pell; Tom W. Meade; Ingrid E. Christophersen; Anke H. Maitland-van der Zee; Ekaterina V. Baranova; Robin Young; Ian Ford; Archie Campbell; Sandosh Padmanabhan; Michiel L. Bots; Diederick E. Grobbee; Philippe Froguel; Dorothée Thuillier; Ronan Roussel; Amélie Bonnefond; Bertrand Cariou; Melissa C. Smart; Yanchun Bao; Meena Kumari; Anubha Mahajan; Jemma C. Hopewell; Sudha Seshadri; Caroline Dale; Rui Bebiano Da Providencia E Costa; Paul M. Ridker; Daniel I. Chasman; Alexander P. Reiner; Marylyn D. Ritchie; Leslie A. Lange; Alex J. Cornish; Sara E. Dobbins; Kari Hemminki; Ben Kinnersley; Marc Sanson; Karim Labreche; Matthias Simon; Melissa L. Bondy; Philip J. Law; Helen E. Speedy; James M. Allan; Ni Li; Molly Went; Niels Weinhold; Gareth J. Morgan; Pieter Sonneveld; Björn Nilsson; Hartmut Goldschmidt; Amit Sud; Andreas Engert; Markus Hansson; Harry Hemingway; Folkert W. Asselbergs; Riyaz S. Patel; Brendan J. Keating; Naveed Sattar; Richard S. Houlston; Juan P. Casas; Aroon D. Hingorani;doi: 10.1101/329052 , 10.1186/s12872-019-1187-z , 10.17863/cam.59255 , 10.17863/cam.43205 , 10.7892/boris.137329
pmc: PMC6820948
pmid: 31664920
doi: 10.1101/329052 , 10.1186/s12872-019-1187-z , 10.17863/cam.59255 , 10.17863/cam.43205 , 10.7892/boris.137329
pmc: PMC6820948
pmid: 31664920
AbstractBackgroundWe characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.MethodsPublished and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Fourteen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentrationResultsThe PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95%CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95%CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95%CI 0.57; 1.22) for the GS, compared to 0.85 (95%CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95%CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable.ConclusionsGenetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. Apparent discordance between genetic associations and trial outcome for T2DM might be explained lack by a of statistical precision, or differences in the nature and duration of genetic versus pharmacological perturbation of PCSK9.FundingThis research was funded by the British Heart Foundation (SP/13/6/30554, RG/10/12/28456, FS/18/23/33512), UCL Hospitals NIHR Biomedical Research Centre, by the Rosetrees and Stoneygate Trusts.Condensed abstractEvidence on the long-term efficacy and safety of therapeutic inhibition of PCSK9 is lacking. To explore potential long-term effects of PCSK9 inhibition, we characterised the phenotypic consequence of LDL-cholesterol lowering variants at the PCSK9 locus. A PCSK9 gene score comprising 4 SNPs recapitulated the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and risk of myocardial infarction, and was associated with an increased risk of type 2 diabetes. No associations with safety outcomes such as cancer, COPD, Alzheimer’s disease or atrial fibrillation were identified. Our findings suggest PCSK9 inhibition may be safe and effective during prolonged use.
Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2019Full-Text: http://europepmc.org/articles/PMC6820948Data sources: PubMed CentralOxford University Research Archive; BMC Cardiovascular Disorders; UnissResearchOther literature type . Article . 2019 . Peer-reviewedLicense: CC BYNARCIS; BMC Cardiovascular DisordersArticle . 2019bioRxivPreprint . 2018Spiral - Imperial College Digital RepositoryArticle . 2019Data sources: Spiral - Imperial College Digital RepositoryCopenhagen University Research Information SystemArticle . 2019Data sources: Copenhagen University Research Information SystemLUMC Scholarly Publications; NARCISOther literature type . Article . 2019UniSA Research Outputs RepositoryArticle . 2019 . Peer-reviewedData sources: UniSA Research Outputs Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
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For further information contact us at helpdesk@openaire.euAccess RoutesGreen gold 30 citations 30 popularity Top 10% influence Average impulse Top 10% Powered by BIP!visibility 11visibility views 11 download downloads 26 Powered bymore_vert Archivio Istituziona... arrow_drop_down Europe PubMed CentralArticle . 2019Full-Text: http://europepmc.org/articles/PMC6820948Data sources: PubMed CentralOxford University Research Archive; BMC Cardiovascular Disorders; UnissResearchOther literature type . Article . 2019 . Peer-reviewedLicense: CC BYNARCIS; BMC Cardiovascular DisordersArticle . 2019bioRxivPreprint . 2018Spiral - Imperial College Digital RepositoryArticle . 2019Data sources: Spiral - Imperial College Digital RepositoryCopenhagen University Research Information SystemArticle . 2019Data sources: Copenhagen University Research Information SystemLUMC Scholarly Publications; NARCISOther literature type . Article . 2019UniSA Research Outputs RepositoryArticle . 2019 . Peer-reviewedData sources: UniSA Research Outputs Repositoryadd ClaimPlease grant OpenAIRE to access and update your ORCID works.This Research product is the result of merged Research products in OpenAIRE.
You have already added works in your ORCID record related to the merged Research product.This Research product is the result of merged Research products in OpenAIRE.
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