Author: "Patel, Riyaz S" / Publisher: uppsala universitet, science for life laboratory, scilifelab - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Patel, Riyaz S"' showing total 20 results

Start Over Author "Patel, Riyaz S" Publisher uppsala universitet, science for life laboratory, scilifelab

20 results on '"Patel, Riyaz S"'

1. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Author: Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., Leander, Karin, Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., and Leander, Karin
Abstract: Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intro
Published: 2022
Full Text: View/download PDF

2. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Author: Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., Leander, Karin, Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., and Leander, Karin
Abstract: Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intro
Published: 2022
Full Text: View/download PDF

3. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Author: Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., Leander, Karin, Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., and Leander, Karin
Abstract: Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intro
Published: 2022
Full Text: View/download PDF

4. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Author: Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., Leander, Karin, Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., and Leander, Karin
Abstract: Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intro
Published: 2022
Full Text: View/download PDF

5. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

Author: Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., Leander, Karin, Schillemans, Tessa, Tragante, Vinicius, Maitusong, Buamina, Gigante, Bruna, Cresci, Sharon, Laguzzi, Federica, Vikstrom, Max, Richards, Mark, Pilbrow, Anna, Cameron, Vicky, Foco, Luisa, Doughty, Robert N., Kuukasjarvi, Pekka, Allayee, Hooman, Hartiala, Jaana A., Tang, W. H. Wilson, Lyytikainen, Leo-Pekka, Nikus, Kjell, Laurikka, Jari O., Srinivasan, Sundararajan, Mordi, Ify R., Trompet, Stella, Kraaijeveld, Adriaan, van Setten, Jessica, Gijsberts, Crystel M., Maitland-van der Zee, Anke H., Saely, Christoph H., Gong, Yan, Johnson, Julie A., Cooper-DeHoff, Rhonda M., Pepine, Carl J., Casu, Gavino, Leiherer, Andreas, Drexel, Heinz, Horne, Benjamin D., van der Laan, Sander W., Marziliano, Nicola, Hazen, Stanley L., Sinisalo, Juha, Kahonen, Mika, Lehtimaki, Terho, Lang, Chim C., Burkhardt, Ralph, Scholz, Markus, Jukema, J. Wouter, Eriksson, Niclas, Åkerblom, Axel, James, Stefan, Held, Claes, Hagström, Emil, Spertus, John A., Algra, Ale, de Faire, Ulf, Akesson, Agneta, Asselbergs, Folkert W., Patel, Riyaz S., and Leander, Karin
Abstract: Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98-1.05 and rs7672915, HR: 0.97, 95% CI 0.94-1.00; rs3755863, HR: 1.02, 95% CI 0.99-1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intro
Published: 2022
Full Text: View/download PDF

6. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author: Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.
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.
Published: 2019
Full Text: View/download PDF

7. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author: Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.
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.
Published: 2019
Full Text: View/download PDF

8. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author: Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.
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.
Published: 2019
Full Text: View/download PDF

9. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author: Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.
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.
Published: 2019
Full Text: View/download PDF

10. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Author: Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., Hingorani, Aroon D., Schmidt, Amand F., Holmes, Michael V., Preiss, David, Swerdlow, Daniel I., Denaxas, Spiros, Fatemifar, Ghazaleh, Faraway, Rupert, Finan, Chris, Valentine, Dennis, Fairhurst-Hunter, Zammy, Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Lill, Christina M., Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert A., Luan, Jian'an, Bobak, Martin, Malyutina, Sofia, Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Jess, Tine, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Lester, Kirchner H., Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Scott, Rodney, Schofield, Peter, O'Donnell, Martin, Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, D. O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Meade, Tom, Christophersen, Ingrid E., Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Roussel, Ronan, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Hopewell, Jemma C., Seshadri, Sudha, Dale, Caroline, Costa, Rui Providencia E., Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Ritchie, Marylyn D., Lange, Leslie A., Cornish, Alex J., Dobbins, Sara E., Hemminki, Kari, Kinnersley, Ben, Sanson, Marc, Labreche, Karim, Simon, Matthias, Bondy, Melissa, Law, Philip, Speedy, Helen, Allan, James, Li, Ni, Went, Molly, Weinhold, Niels, Morgan, Gareth, Sonneveld, Pieter, Nilsson, Bjorn, Goldschmidt, Hartmut, Sud, Amit, Engert, Andreas, Hansson, Markus, Hemingway, Harry, Asselbergs, Folkert W., Patel, Riyaz S., Keating, Brendan J., Sattar, Naveed, Houlston, Richard, Casas, Juan P., and Hingorani, Aroon D.
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.
Published: 2019
Full Text: View/download PDF

11. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

Author: Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed
Abstract: 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 off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects 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, HbA 1c, 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 HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -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 benefi ts of PCSK9 inhibi
Published: 2017
Full Text: View/download PDF

12. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

Author: Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed
Abstract: 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 off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects 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, HbA 1c, 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 HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -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 benefi ts of PCSK9 inhibi
Published: 2017
Full Text: View/download PDF

13. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

Author: Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed
Abstract: 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 off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects 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, HbA 1c, 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 HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -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 benefi ts of PCSK9 inhibi
Published: 2017
Full Text: View/download PDF

14. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

Author: Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed
Abstract: 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 off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects 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, HbA 1c, 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 HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -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 benefi ts of PCSK9 inhibi
Published: 2017
Full Text: View/download PDF

15. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

Author: Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., Sattar, Naveed, Schmidt, Amand F., Swerdlow, Daniel I., Holmes, Michael V., Patel, Riyaz S., Fairhurst-Hunter, Zammy, Lyall, Donald M., Hartwig, Fernando Pires, Horta, Bernardo Lessa, Hypponen, Elina, Power, Christine, Moldovan, Max, van Iperen, Erik, Hovingh, G. Kees, Demuth, Ilja, Norman, Kristina, Steinhagen-Thiessen, Elisabeth, Demuth, Juri, Bertram, Lars, Liu, Tian, Coassin, Stefan, Willeit, Johann, Kiechl, Stefan, Willeit, Karin, Mason, Dan, Wright, John, Morris, Richard, Wanamethee, Goya, Whincup, Peter, Ben-Shlomo, Yoav, McLachlan, Stela, Price, Jackie F., Kivimaki, Mika, Welch, Catherine, Sanchez-Galvez, Adelaida, Marques-Vidal, Pedro, Nicolaides, Andrew, Panayiotou, Andrie G., Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Matullo, Giuseppe, Fiorito, Giovanni, Guarrera, Simonetta, Sacerdote, Carlotta, Wareham, Nicholas J., Langenberg, Claudia, Scott, Robert, Luan, Jian'an, Bobak, Martin, Malyutina, Sofi A., Pajak, Andrzej, Kubinova, Ruzena, Tamosiunas, Abdonas, Pikhart, Hynek, Husemoen, Lise Lotte Nystrup, Grarup, Niels, Pedersen, Oluf, Hansen, Torben, Linneberg, Allan, Simonsen, Kenneth Starup, Cooper, Jackie, Humphries, Steve E., Brilliant, Murray, Kitchner, Terrie, Hakonarson, Hakon, Carrell, David S., McCarty, Catherine A., Kirchner, H. Lester, Larson, Eric B., Crosslin, David R., de Andrade, Mariza, Roden, Dan M., Denny, Joshua C., Carty, Cara, Hancock, Stephen, Attia, John, Holliday, Elizabeth, Donnell, Martin O', Yusuf, Salim, Chong, Michael, Pare, Guillaume, van der Harst, Pim, Said, M. Abdullah, Eppinga, Ruben N., Verweij, Niek, Snieder, Harold, Christen, Tim, Mook-Kanamori, Dennis O., Gustafsson, Stefan, Lind, Lars, Ingelsson, Erik, Pazoki, Raha, Franco, Oscar, Hofman, Albert, Uitterlinden, Andre, Dehghan, Abbas, Teumer, Alexander, Baumeister, Sebastian, Doerr, Marcus, Lerch, Markus M., Voelker, Uwe, Voelzke, Henry, Ward, Joey, Pell, Jill P., Smith, Daniel J., Meade, Tom, Maitland-van der Zee, Anke H., Baranova, Ekaterina V., Young, Robin, Ford, Ian, Campbell, Archie, Padmanabhan, Sandosh, Bots, Michiel L., Grobbee, Diederick E., Froguel, Philippe, Thuillier, Dorothee, Balkau, Beverley, Bonnefond, Amelie, Cariou, Bertrand, Smart, Melissa, Bao, Yanchun, Kumari, Meena, Mahajan, Anubha, Ridker, Paul M., Chasman, Daniel I., Reiner, Alex P., Lange, Leslie A., Ritchie, Marylyn D., Asselbergs, Folkert W., Casas, Juan-Pablo, Keating, Brendan J., Preiss, David, Hingorani, Aroon D., and Sattar, Naveed
Abstract: 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 off sets their substantial benefi ts. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely eff ects 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, HbA 1c, 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 HbA 1c (0.03%, -0.01 to 0.08), fasting insulin (0.00%, -0.06 to 0.07), and BMI (0.11 kg/m(2), -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 benefi ts of PCSK9 inhibi
Published: 2017
Full Text: View/download PDF

16. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Author: van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., Asselbergs, Folkert W., van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., and Asselbergs, Folkert W.
Abstract: BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD., De två första författarna delar förstaförfattarskapet.
Published: 2016
Full Text: View/download PDF

17. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Author: van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., Asselbergs, Folkert W., van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., and Asselbergs, Folkert W.
Abstract: BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD., De två första författarna delar förstaförfattarskapet.
Published: 2016
Full Text: View/download PDF

18. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Author: van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., Asselbergs, Folkert W., van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., and Asselbergs, Folkert W.
Abstract: BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD., De två första författarna delar förstaförfattarskapet.
Published: 2016
Full Text: View/download PDF

19. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Author: van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., Asselbergs, Folkert W., van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., and Asselbergs, Folkert W.
Abstract: BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD., De två första författarna delar förstaförfattarskapet.
Published: 2016
Full Text: View/download PDF

20. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Author: van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., Asselbergs, Folkert W., van der Laan, Sander W., Fall, Tove, Soumare, Aicha, Teumer, Alexander, Sedaghat, Sanaz, Baumert, Jens, Zabaneh, Delilah, van Setten, Jessica, Isgum, Ivana, Galesloot, Tessel E., Arpegard, Johannes, Amouyel, Philippe, Trompet, Stella, Waldenberger, Melanie, Doerr, Marcus, Magnusson, Patrik K., Giedraitis, Vilmantas, Larsson, Anders, Morris, Andrew P., Felix, Janine F., Morrison, Alanna C., Franceschini, Nora, Bis, Joshua C., Kavousi, Maryam, O'Donnell, Christopher, Drenos, Fotios, Tragante, Vinicius, Munroe, Patricia B., Malik, Rainer, Dichgans, Martin, Worrall, Bradford B., Erdmann, Jeanette, Nelson, Christopher P., Samani, Nilesh J., Schunkert, Heribert, Marchini, Jonathan, Patel, Riyaz S., Hingorani, Aroon D., Lind, Lars, Pedersen, Nancy L., de Graaf, Jacqueline, Kiemeney, Lambertus A. L. M., Baumeister, Sebastian E., Franco, Oscar H., Hofman, Albert, Uitterlinden, Andre G., Koenig, Wolfgang, Meisinger, Christa, Peters, Annette, Thorand, Barbara, Jukema, J. Wouter, Eriksen, Bjorn Odvar, Toft, Ingrid, Wilsgaard, Tom, Onland-Moret, N. Charlotte, van der Schouw, Yvonne T., Debette, Stephanie, Kumari, Meena, Svensson, Per, van der Harst, Pim, Kivimaki, Mika, Keating, Brendan J., Sattar, Naveed, Dehghan, Abbas, Reiner, Alex P., Ingelsson, Erik, den Ruijter, Hester M., de Bakker, Paul I. W., Pasterkamp, Gerard, Ärnlöv, Johan, Holmes, Michael V., and Asselbergs, Folkert W.
Abstract: BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD., De två första författarna delar förstaförfattarskapet.
Published: 2016
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

20 results on '"Patel, Riyaz S"'

1. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

2. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

3. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

4. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

5. Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease : An Individual-Level Meta-Analysis

6. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

7. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

8. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

9. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

10. Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

11. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

12. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

13. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

14. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

15. PCSK9 genetic variants and risk of type 2 diabetes : a mendelian randomisation study

16. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

17. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

18. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

19. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

20. Cystatin C and Cardiovascular Disease : A Mendelian Randomization Study

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Publication Year Range

Publication Type

Database

Publisher

20 results on '"Patel, Riyaz S"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources