dc.contributor.author | Schmidt, Amand F | |
dc.contributor.author | Holmes, Michael V | |
dc.contributor.author | Preiss, David | |
dc.contributor.author | Swerdlow, Daniel I | |
dc.contributor.author | Denaxas, Spiros | |
dc.contributor.author | Fatemifar, Ghazaleh | |
dc.contributor.author | Faraway, Rupert | |
dc.contributor.author | Finan, Chris | |
dc.contributor.author | Valentine, Dennis | |
dc.contributor.author | Fairhurst-Hunter, Zammy | |
dc.contributor.author | Hartwig, Fernando P | |
dc.contributor.author | Horta, Bernardo L | |
dc.contributor.author | Hypponen, Elina | |
dc.contributor.author | Power, Christine | |
dc.contributor.author | Moldovan, Max | |
dc.contributor.author | van Iperen, Erik | |
dc.contributor.author | Hovingh, Kees | |
dc.contributor.author | Demuth, Ilja | |
dc.contributor.author | Norman, Kristina | |
dc.contributor.author | Steinhagen-Thiessen, Elisabeth | |
dc.contributor.author | Demuth, Juri | |
dc.contributor.author | Bertram, Lars | |
dc.contributor.author | Lill, Christina M | |
dc.contributor.author | Coassin, Stefan | |
dc.contributor.author | Willeit, Johann | |
dc.contributor.author | Kiechl, Stefan | |
dc.contributor.author | Willeit, Karin | |
dc.contributor.author | Mason, Dan | |
dc.contributor.author | Wright, John | |
dc.contributor.author | Morris, Richard | |
dc.contributor.author | Wanamethee, Goya | |
dc.contributor.author | Whincup, Peter | |
dc.contributor.author | Ben-Shlomo, Yoav | |
dc.contributor.author | McLachlan, Stela | |
dc.contributor.author | Price, Jackie F | |
dc.contributor.author | Kivimaki, Mika | |
dc.contributor.author | Welch, Catherine | |
dc.contributor.author | Sanchez-Galvez, Adelaida | |
dc.contributor.author | Marques-Vidal, Pedro | |
dc.contributor.author | Nicolaides, Andrew | |
dc.contributor.author | Panayiotou, Andrie G | |
dc.contributor.author | Onland-Moret, N. C | |
dc.contributor.author | van der Schouw, Yvonne T | |
dc.contributor.author | Matullo, Giuseppe | |
dc.contributor.author | Fiorito, Giovanni | |
dc.contributor.author | Guarrera, Simonetta | |
dc.contributor.author | Sacerdote, Carlotta | |
dc.contributor.author | Wareham, Nicholas J | |
dc.contributor.author | Langenberg, Claudia | |
dc.contributor.author | Scott, Robert A | |
dc.contributor.author | Luan, Jian’an | |
dc.contributor.author | Bobak, Martin | |
dc.contributor.author | Malyutina, Sofia | |
dc.contributor.author | Pająk, Andrzej | |
dc.contributor.author | Kubinova, Ruzena | |
dc.contributor.author | Tamosiunas, Abdonas | |
dc.contributor.author | Pikhart, Hynek | |
dc.contributor.author | Grarup, Niels | |
dc.contributor.author | Pedersen, Oluf | |
dc.contributor.author | Hansen, Torben | |
dc.contributor.author | Linneberg, Allan | |
dc.contributor.author | Jess, Tine | |
dc.contributor.author | Cooper, Jackie | |
dc.contributor.author | Humphries, Steve E | |
dc.contributor.author | Brilliant, Murray | |
dc.contributor.author | Kitchner, Terrie | |
dc.contributor.author | Hakonarson, Hakon | |
dc.contributor.author | Carrell, David S | |
dc.contributor.author | McCarty, Catherine A | |
dc.contributor.author | Lester, Kirchner H | |
dc.contributor.author | Larson, Eric B | |
dc.contributor.author | Crosslin, David R | |
dc.contributor.author | de Andrade, Mariza | |
dc.contributor.author | Roden, Dan M | |
dc.contributor.author | Denny, Joshua C | |
dc.contributor.author | Carty, Cara | |
dc.contributor.author | Hancock, Stephen | |
dc.contributor.author | Attia, John | |
dc.contributor.author | Holliday, Elizabeth | |
dc.contributor.author | Scott, Rodney | |
dc.contributor.author | Schofield, Peter | |
dc.contributor.author | O’Donnell, Martin | |
dc.contributor.author | Yusuf, Salim | |
dc.contributor.author | Chong, Michael | |
dc.contributor.author | Pare, Guillaume | |
dc.contributor.author | van der Harst, Pim | |
dc.contributor.author | Said, M. A | |
dc.contributor.author | Eppinga, Ruben N | |
dc.contributor.author | Verweij, Niek | |
dc.contributor.author | Snieder, Harold | |
dc.contributor.author | Christen, Tim | |
dc.contributor.author | Mook-Kanamori, D. O | |
dc.contributor.author | Gustafsson, Stefan | |
dc.contributor.author | Lind, Lars | |
dc.contributor.author | Ingelsson, Erik | |
dc.contributor.author | Pazoki, Raha | |
dc.contributor.author | Franco, Oscar | |
dc.contributor.author | Hofman, Albert | |
dc.contributor.author | Uitterlinden, Andre | |
dc.contributor.author | Dehghan, Abbas | |
dc.contributor.author | Teumer, Alexander | |
dc.contributor.author | Baumeister, Sebastian | |
dc.contributor.author | Dörr, Marcus | |
dc.contributor.author | Lerch, Markus M | |
dc.contributor.author | Völker, Uwe | |
dc.contributor.author | Völzke, Henry | |
dc.contributor.author | Ward, Joey | |
dc.contributor.author | Pell, Jill P | |
dc.contributor.author | Meade, Tom | |
dc.contributor.author | Christophersen, Ingrid E | |
dc.contributor.author | Maitland-van der Zee, Anke H | |
dc.contributor.author | Baranova, Ekaterina V | |
dc.contributor.author | Young, Robin | |
dc.contributor.author | Ford, Ian | |
dc.contributor.author | Campbell, Archie | |
dc.contributor.author | Padmanabhan, Sandosh | |
dc.contributor.author | Bots, Michiel L | |
dc.contributor.author | Grobbee, Diederick E | |
dc.contributor.author | Froguel, Philippe | |
dc.contributor.author | Thuillier, Dorothée | |
dc.contributor.author | Roussel, Ronan | |
dc.contributor.author | Bonnefond, Amélie | |
dc.contributor.author | Cariou, Bertrand | |
dc.contributor.author | Smart, Melissa | |
dc.contributor.author | Bao, Yanchun | |
dc.contributor.author | Kumari, Meena | |
dc.contributor.author | Mahajan, Anubha | |
dc.contributor.author | Hopewell, Jemma C | |
dc.contributor.author | Seshadri, Sudha | |
dc.contributor.author | Dale, Caroline | |
dc.contributor.author | Costa, Rui P E | |
dc.contributor.author | Ridker, Paul M | |
dc.contributor.author | Chasman, Daniel I | |
dc.contributor.author | Reiner, Alex P | |
dc.contributor.author | Ritchie, Marylyn D | |
dc.contributor.author | Lange, Leslie A | |
dc.contributor.author | Cornish, Alex J | |
dc.contributor.author | Dobbins, Sara E | |
dc.contributor.author | Hemminki, Kari | |
dc.contributor.author | Kinnersley, Ben | |
dc.contributor.author | Sanson, Marc | |
dc.contributor.author | Labreche, Karim | |
dc.contributor.author | Simon, Matthias | |
dc.contributor.author | Bondy, Melissa | |
dc.contributor.author | Law, Philip | |
dc.contributor.author | Speedy, Helen | |
dc.contributor.author | Allan, James | |
dc.contributor.author | Li, Ni | |
dc.contributor.author | Went, Molly | |
dc.contributor.author | Weinhold, Niels | |
dc.contributor.author | Morgan, Gareth | |
dc.contributor.author | Sonneveld, Pieter | |
dc.contributor.author | Nilsson, Björn | |
dc.contributor.author | Goldschmidt, Hartmut | |
dc.contributor.author | Sud, Amit | |
dc.contributor.author | Engert, Andreas | |
dc.contributor.author | Hansson, Markus | |
dc.contributor.author | Hemingway, Harry | |
dc.contributor.author | Asselbergs, Folkert W | |
dc.contributor.author | Patel, Riyaz S | |
dc.contributor.author | Keating, Brendan J | |
dc.contributor.author | Sattar, Naveed | |
dc.contributor.author | Houlston, Richard | |
dc.contributor.author | Casas, Juan P | |
dc.contributor.author | Hingorani, Aroon D | |
dc.date.accessioned | 2019-11-05T06:02:33Z | |
dc.date.available | 2019-11-05T06:02:33Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | BMC Cardiovascular Disorders. 2019 Oct 29;19(1):240 | |
dc.identifier.uri | http://hdl.handle.net/10852/70726 | |
dc.description.abstract | Background
We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.
Methods
Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen 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 concentration.
Results
The 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.
Conclusions
Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate. | |
dc.language.iso | eng | |
dc.rights | The Author(s). | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9 | |
dc.type | Journal article | |
dc.date.updated | 2019-11-05T06:02:34Z | |
dc.creator.author | Schmidt, Amand F | |
dc.creator.author | Holmes, Michael V | |
dc.creator.author | Preiss, David | |
dc.creator.author | Swerdlow, Daniel I | |
dc.creator.author | Denaxas, Spiros | |
dc.creator.author | Fatemifar, Ghazaleh | |
dc.creator.author | Faraway, Rupert | |
dc.creator.author | Finan, Chris | |
dc.creator.author | Valentine, Dennis | |
dc.creator.author | Fairhurst-Hunter, Zammy | |
dc.creator.author | Hartwig, Fernando P | |
dc.creator.author | Horta, Bernardo L | |
dc.creator.author | Hypponen, Elina | |
dc.creator.author | Power, Christine | |
dc.creator.author | Moldovan, Max | |
dc.creator.author | van Iperen, Erik | |
dc.creator.author | Hovingh, Kees | |
dc.creator.author | Demuth, Ilja | |
dc.creator.author | Norman, Kristina | |
dc.creator.author | Steinhagen-Thiessen, Elisabeth | |
dc.creator.author | Demuth, Juri | |
dc.creator.author | Bertram, Lars | |
dc.creator.author | Lill, Christina M | |
dc.creator.author | Coassin, Stefan | |
dc.creator.author | Willeit, Johann | |
dc.creator.author | Kiechl, Stefan | |
dc.creator.author | Willeit, Karin | |
dc.creator.author | Mason, Dan | |
dc.creator.author | Wright, John | |
dc.creator.author | Morris, Richard | |
dc.creator.author | Wanamethee, Goya | |
dc.creator.author | Whincup, Peter | |
dc.creator.author | Ben-Shlomo, Yoav | |
dc.creator.author | McLachlan, Stela | |
dc.creator.author | Price, Jackie F | |
dc.creator.author | Kivimaki, Mika | |
dc.creator.author | Welch, Catherine | |
dc.creator.author | Sanchez-Galvez, Adelaida | |
dc.creator.author | Marques-Vidal, Pedro | |
dc.creator.author | Nicolaides, Andrew | |
dc.creator.author | Panayiotou, Andrie G | |
dc.creator.author | Onland-Moret, N. C | |
dc.creator.author | van der Schouw, Yvonne T | |
dc.creator.author | Matullo, Giuseppe | |
dc.creator.author | Fiorito, Giovanni | |
dc.creator.author | Guarrera, Simonetta | |
dc.creator.author | Sacerdote, Carlotta | |
dc.creator.author | Wareham, Nicholas J | |
dc.creator.author | Langenberg, Claudia | |
dc.creator.author | Scott, Robert A | |
dc.creator.author | Luan, Jian’an | |
dc.creator.author | Bobak, Martin | |
dc.creator.author | Malyutina, Sofia | |
dc.creator.author | Pająk, Andrzej | |
dc.creator.author | Kubinova, Ruzena | |
dc.creator.author | Tamosiunas, Abdonas | |
dc.creator.author | Pikhart, Hynek | |
dc.creator.author | Grarup, Niels | |
dc.creator.author | Pedersen, Oluf | |
dc.creator.author | Hansen, Torben | |
dc.creator.author | Linneberg, Allan | |
dc.creator.author | Jess, Tine | |
dc.creator.author | Cooper, Jackie | |
dc.creator.author | Humphries, Steve E | |
dc.creator.author | Brilliant, Murray | |
dc.creator.author | Kitchner, Terrie | |
dc.creator.author | Hakonarson, Hakon | |
dc.creator.author | Carrell, David S | |
dc.creator.author | McCarty, Catherine A | |
dc.creator.author | Lester, Kirchner H | |
dc.creator.author | Larson, Eric B | |
dc.creator.author | Crosslin, David R | |
dc.creator.author | de Andrade, Mariza | |
dc.creator.author | Roden, Dan M | |
dc.creator.author | Denny, Joshua C | |
dc.creator.author | Carty, Cara | |
dc.creator.author | Hancock, Stephen | |
dc.creator.author | Attia, John | |
dc.creator.author | Holliday, Elizabeth | |
dc.creator.author | Scott, Rodney | |
dc.creator.author | Schofield, Peter | |
dc.creator.author | O’Donnell, Martin | |
dc.creator.author | Yusuf, Salim | |
dc.creator.author | Chong, Michael | |
dc.creator.author | Pare, Guillaume | |
dc.creator.author | van der Harst, Pim | |
dc.creator.author | Said, M. A | |
dc.creator.author | Eppinga, Ruben N | |
dc.creator.author | Verweij, Niek | |
dc.creator.author | Snieder, Harold | |
dc.creator.author | Christen, Tim | |
dc.creator.author | Mook-Kanamori, D. O | |
dc.creator.author | Gustafsson, Stefan | |
dc.creator.author | Lind, Lars | |
dc.creator.author | Ingelsson, Erik | |
dc.creator.author | Pazoki, Raha | |
dc.creator.author | Franco, Oscar | |
dc.creator.author | Hofman, Albert | |
dc.creator.author | Uitterlinden, Andre | |
dc.creator.author | Dehghan, Abbas | |
dc.creator.author | Teumer, Alexander | |
dc.creator.author | Baumeister, Sebastian | |
dc.creator.author | Dörr, Marcus | |
dc.creator.author | Lerch, Markus M | |
dc.creator.author | Völker, Uwe | |
dc.creator.author | Völzke, Henry | |
dc.creator.author | Ward, Joey | |
dc.creator.author | Pell, Jill P | |
dc.creator.author | Meade, Tom | |
dc.creator.author | Christophersen, Ingrid E | |
dc.creator.author | Maitland-van der Zee, Anke H | |
dc.creator.author | Baranova, Ekaterina V | |
dc.creator.author | Young, Robin | |
dc.creator.author | Ford, Ian | |
dc.creator.author | Campbell, Archie | |
dc.creator.author | Padmanabhan, Sandosh | |
dc.creator.author | Bots, Michiel L | |
dc.creator.author | Grobbee, Diederick E | |
dc.creator.author | Froguel, Philippe | |
dc.creator.author | Thuillier, Dorothée | |
dc.creator.author | Roussel, Ronan | |
dc.creator.author | Bonnefond, Amélie | |
dc.creator.author | Cariou, Bertrand | |
dc.creator.author | Smart, Melissa | |
dc.creator.author | Bao, Yanchun | |
dc.creator.author | Kumari, Meena | |
dc.creator.author | Mahajan, Anubha | |
dc.creator.author | Hopewell, Jemma C | |
dc.creator.author | Seshadri, Sudha | |
dc.creator.author | Dale, Caroline | |
dc.creator.author | Costa, Rui P E | |
dc.creator.author | Ridker, Paul M | |
dc.creator.author | Chasman, Daniel I | |
dc.creator.author | Reiner, Alex P | |
dc.creator.author | Ritchie, Marylyn D | |
dc.creator.author | Lange, Leslie A | |
dc.creator.author | Cornish, Alex J | |
dc.creator.author | Dobbins, Sara E | |
dc.creator.author | Hemminki, Kari | |
dc.creator.author | Kinnersley, Ben | |
dc.creator.author | Sanson, Marc | |
dc.creator.author | Labreche, Karim | |
dc.creator.author | Simon, Matthias | |
dc.creator.author | Bondy, Melissa | |
dc.creator.author | Law, Philip | |
dc.creator.author | Speedy, Helen | |
dc.creator.author | Allan, James | |
dc.creator.author | Li, Ni | |
dc.creator.author | Went, Molly | |
dc.creator.author | Weinhold, Niels | |
dc.creator.author | Morgan, Gareth | |
dc.creator.author | Sonneveld, Pieter | |
dc.creator.author | Nilsson, Björn | |
dc.creator.author | Goldschmidt, Hartmut | |
dc.creator.author | Sud, Amit | |
dc.creator.author | Engert, Andreas | |
dc.creator.author | Hansson, Markus | |
dc.creator.author | Hemingway, Harry | |
dc.creator.author | Asselbergs, Folkert W | |
dc.creator.author | Patel, Riyaz S | |
dc.creator.author | Keating, Brendan J | |
dc.creator.author | Sattar, Naveed | |
dc.creator.author | Houlston, Richard | |
dc.creator.author | Casas, Juan P | |
dc.creator.author | Hingorani, Aroon D | |
dc.identifier.cristin | 1763995 | |
dc.identifier.doi | https://doi.org/10.1186/s12872-019-1187-z | |
dc.identifier.urn | URN:NBN:no-73853 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/70726/1/12872_2019_Article_1187.pdf | |
dc.type.version | PublishedVersion | |
cristin.articleid | 240 | |