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23 results on '"Thorgeirsson, Guðmundur"'

1. Genome-wide association analysis provides insights into the molecular etiology of dilated cardiomyopathy

Author

Zheng, Sean L., Henry, Albert, Cannie, Douglas, Lee, Michael, Miller, David, McGurk, Kathryn A., Bond, Isabelle, Xu, Xiao, Issa, Hanane, Francis, Catherine, De Marvao, Antonio, Theotokis, Pantazis I., Buchan, Rachel J., Speed, Doug, Abner, Erik, Adams, Lance, Aragam, Krishna G., Ärnlöv, Johan, Raja, Anna Axelsson, Backman, Joshua D., Baksi, John, Barton, Paul J. R., Biddinger, Kiran J., Boersma, Eric, Brandimarto, Jeffrey, Brunak, Søren, Bundgaard, Henning, Carey, David J., Charron, Philippe, Cook, James P., Cook, Stuart A., Denaxas, Spiros, Deleuze, Jean-François, Doney, Alexander S., Elliott, Perry, Erikstrup, Christian, Esko, Tõnu, Farber-Eger, Eric H., Finan, Chris, Garnier, Sophie, Ghouse, Jonas, Giedraitis, Vilmantas, Guðbjartsson, Daniel F., Haggerty, Christopher M., Halliday, Brian P., Helgadottir, Anna, Hemingway, Harry, Hillege, Hans L., Kardys, Isabella, Lind, Lars, Lindgren, Cecilia M., Lowery, Brandon D., Manisty, Charlotte, Margulies, Kenneth B., Moon, James C., Mordi, Ify R., Morley, Michael P., Morris, Andrew D., Morris, Andrew P., Morton, Lori, Noursadeghi, Mahdad, Ostrowski, Sisse R., Owens, Anjali T., Palmer, Colin N. A., Pantazis, Antonis, Pedersen, Ole B. V., Prasad, Sanjay K., Shekhar, Akshay, Smelser, Diane T., Srinivasan, Sundararajan, Stefansson, Kari, Sveinbjörnsson, Garðar, Syrris, Petros, Tammesoo, Mari-Liis, Tayal, Upasana, Teder-Laving, Maris, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Tragante, Vinicius, Trégouët, David-Alexandre, Treibel, Thomas A., Ullum, Henrik, Valdes, Ana M., van Setten, Jessica, van Vugt, Marion, Veluchamy, Abirami, Verschuren, W. M. Monique, Villard, Eric, Yang, Yifan, Asselbergs, Folkert W., Cappola, Thomas P., Dube, Marie-Pierre, Dunn, Michael E., Ellinor, Patrick T., Hingorani, Aroon D., Lang, Chim C., Samani, Nilesh J., Shah, Svati H., Smith, J. Gustav, Vasan, Ramachandran S., O’Regan, Declan P., Holm, Hilma, Noseda, Michela, Wells, Quinn, Ware, James S., and Lumbers, R. Thomas

Published
2024
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3. Large-Scale Screening for Monogenic and Clinically Defined Familial Hypercholesterolemia in Iceland

Author

Björnsson, Eythór, primary, Thorgeirsson, Guðmundur, additional, Helgadóttir, Anna, additional, Thorleifsson, Guðmar, additional, Sveinbjörnsson, Garðar, additional, Kristmundsdóttir, Snaedís, additional, Jónsson, Hákon, additional, Jónasdóttir, Aðalbjörg, additional, Jónasdóttir, Áslaug, additional, Sigurðsson, Ásgeir, additional, Guðnason, Thórarinn, additional, Ólafsson, Ísleifur, additional, Sigurðsson, Emil L., additional, Sigurðardóttir, Ólöf, additional, Viðarsson, Brynjar, additional, Baldvinsson, Magnús, additional, Bjarnason, Ragnar, additional, Danielsen, Ragnar, additional, Matthíasson, Stefán E., additional, Thórarinsson, Björn L., additional, Grétarsdóttir, Sólveig, additional, Steinthórsdóttir, Valgerður, additional, Halldórsson, Bjarni V., additional, Andersen, Karl, additional, Arnar, Davíð O., additional, Jónsdóttir, Ingileif, additional, Guðbjartsson, Daníel F., additional, Hólm, Hilma, additional, Thorsteinsdóttir, Unnur, additional, Sulem, Patrick, additional, and Stefánsson, Kári, additional

Published
2021
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4. Association of Genetically Predicted Lipid Levels With the Extent of Coronary Atherosclerosis in Icelandic Adults

Author

Björnsson, Eythór, primary, Thorleifsson, Guðmar, additional, Helgadóttir, Anna, additional, Guðnason, Thórarinn, additional, Guðbjartsson, Tómas, additional, Andersen, Karl, additional, Grétarsdóttir, Sólveig, additional, Ólafsson, Ísleifur, additional, Tragante, Vinicius, additional, Ólafsson, Ólafur Hreiðar, additional, Jónsdóttir, Birna, additional, Eyjólfsson, Guðmundur I., additional, Sigurðardóttir, Ólöf, additional, Thorgeirsson, Guðmundur, additional, Guðbjartsson, Daníel F., additional, Thorsteinsdóttir, Unnur, additional, Hólm, Hilma, additional, and Stefánsson, Kári, additional

Published
2020
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5. Endothelial Function Assessed by Peripheral Arterial Tonometry is not related to Cardiovascular Risk Score in Healthy Subjects

Author

Bylgja Rún Stefánsdóttir, Thorgeirsson Guðmundur, Linda B Kristinsdottir, Vilmundur Gudnason, Ylfa Rún Sigurðardóttir, Karl Andersen, and Thor Aspelund

Subjects
Reactive hyperemia index, medicine.medical_specialty, lcsh:Diseases of the circulatory (Cardiovascular) system, CV risk factors, lcsh:Medicine, Peripheral arterial tonometry, Internal medicine, Heart rate, medicine, Myocardial infarction, Endothelial dysfunction, Reactive hyperemia, Framingham Risk Score, Primary prevention, business.industry, lcsh:R, Healthy subjects, Augmentation index, Endothelial function, Baseline pulse amplitude, medicine.disease, Surgery, Peripheral, lcsh:RC666-701, Cohort, CV risk score, Cardiology, business
Abstract

Background: The majority of first cases of myocardial infarction stem from those classified as intermediate- or low-risk in CV risk prediction calculators. Risk prediction models need to be refined in their capacity to discriminate high-risk from low-risk. Peripheral arterial tonometry (PAT) is a non-invasive method to assess peripheral endothelial function that could potentially improve primary prevention of CVD. We investigated the relation of PAT results to CV risk factors and risk score in a healthy cohort.Methods: PAT measurements were performed on 102 individuals, with no previous history of CAD, attending a Risk Preventive Clinic. Traditional CV risk factors were evaluated and integrated into a CV risk score calculator. Outcome was expressed as absolute and relative 10-year risk of developing CVD. Results: PAT results of reactive hyperemia index (RHI) and augmentation index (AI) had no statistically significant relation to risk score while baseline pulse amplitude was positively correlated with both absolute (p = 0.02) and relative (p = 0.02) 10-year risk of developing CVD. Among CV risk factors only heart rate was significantly associated with RHI (r = - 0.24, R2 = 0.06, p = 0.01). AI and baseline pulse amplitude both correlated with several risk factors.Conclusions: Endothelial dysfunction, as measured by PAT, was not associated with an increased 10-year risk of developing CVD. The relation between endothelial dysfunction and established CV risk factors was limited. Further clinical end point studies are needed to fully comprehend the diagnostic and predictive value of PAT measurements in healthy subjects.

Published
2016

6. A frameshift deletion in the sarcomere geneMYL4causes early-onset familial atrial fibrillation

Author

Gudbjartsson, Daniel F., primary, Holm, Hilma, additional, Sulem, Patrick, additional, Masson, Gisli, additional, Oddsson, Asmundur, additional, Magnusson, Olafur Th., additional, Saemundsdottir, Jona, additional, Helgadottir, Hafdis Th., additional, Helgason, Hannes, additional, Johannsdottir, Hrefna, additional, Gretarsdottir, Solveig, additional, Gudjonsson, Sigurjon A., additional, Njølstad, Inger, additional, Løchen, Maja-Lisa, additional, Baum, Larry, additional, Ma, Ronald C.W., additional, Sigfusson, Gunnlaugur, additional, Kong, Augustine, additional, Thorgeirsson, Guðmundur, additional, Sverrisson, Jon Th., additional, Thorsteinsdottir, Unnur, additional, Stefansson, Kari, additional, and Arnar, David O., additional

Published
2016
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7. A frameshift deletion in the sarcomere gene MYL4 causes early-onset familial atrial fibrillation.

Author

Gudbjartsson, Daniel F., Holm, Hilma, Sulem, Patrick, Masson, Gisli, Oddsson, Asmundur, Magnusson, Olafur Th., Saemundsdottir, Jona, Helgadottir, Hafdis Th., Helgason, Hannes, Johannsdottir, Hrefna, Gretarsdottir, Solveig, Gudjonsson, Sigurjon A., Njølstad, Inger, Løchen, Maja-Lisa, Baum, Larry, Ma, Ronald C.W., Sigfusson, Gunnlaugur, Kong, Augustine, Thorgeirsson, Guðmundur, and Sverrisson, Jon Th.

Abstract

Aims: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man, causing substantial morbidity and mortality with a major worldwide public health impact. It is increasingly recognized as a highly heritable condition. This study aimed to determine genetic risk factors for early-onset AF. Methods and results; We sequenced the whole genomes of 8453 Icelanders and imputed genotypes of the 25.5 million sequence variants we discovered into 1799 Icelanders with early-onset AF (diagnosed before 60 years of age) and 337 453 controls. Each sequence variant was tested for association based on multiplicative and recessive inheritance models. We discovered a rare frameshift deletion in the myosin MYL4 gene (c.234delC) that associates with early-onset AF under a recessive mode of inheritance (allelic frequency¼0.58%). We found eight homozygous carriers of the mutation, all of whom had early-onset AF. Six of the homozygotes were diagnosed by the age of 30 and the remaining two in their 50s. Three of the homozygotes had received pacemaker implantations due to sick sinus syndrome, three had suffered an ischemic stroke, and one suffered sudden cardiac death. Conclusions: Through a population approach we found a loss of function mutation in the myosin gene MYL4 that, in the homozygous state, is completely penetrant for early-onset AF. The finding may provide novel mechanistic insight into the pathophysiology of this complex arrhythmia. [ABSTRACT FROM AUTHOR]

Published
2017
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8. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism

Author

Helgadottir, Anna, Gretarsdottir, Solveig, Thorleifsson, Gudmar, Holm, Hilma, Patel, Riyaz S, Gudnason, Thorarinn, Jones, Gregory T, van Rij, Andre M, Eapen, Danny J, Baas, Annette F, Tregouet, David-Alexandre, Morange, Pierre-Emmanuel, Emmerich, Joseph, Lindblad, Bengt, Gottsäter, Anders, Kiemeny, Lambertus A, Lindholt, Jes S., Sakalihasan, Natzi, Ferrell, Robert E, Carey, David J, Elmore, James R, Tsao, Philip S, Grarup, Niels, Jørgensen, Torben, Witte, Daniel R, Hansen, Torben, Pedersen, Oluf, Pola, Roberto, Gaetani, Eleonora, Magnadottir, Hulda B, Wijmenga, Cisca, Tromp, Gerard, Ronkainen, Antti, Ruigrok, Ynte M, Blankensteijn, Jan D, Mueller, Thomas, Wells, Philip S, Corral, Javier, Soria, Jose Manuel, Souto, Juan Carlos, Peden, John F, Jalilzadeh, Shapour, Mayosi, Bongani M, Keavney, Bernard, Strawbridge, Rona J, Sabater-Lleal, Maria, Gertow, Karl, Baldassarre, Damiano, Nyyssönen, Kristiina, Rauramaa, Rainer, Smit, Andries J, Mannarino, Elmo, Giral, Philippe, Tremoli, Elena, de Faire, Ulf, Humphries, Steve E, Hamsten, Anders, Haraldsdottir, Vilhelmina, Olafsson, Isleifur, Magnusson, Magnus K, Samani, Nilesh J, Levey, Allan I, Markus, Hugh S, Kostulas, Konstantinos, Dichgans, Martin, Berger, Klaus, Kuhlenbäumer, Gregor, Ringelstein, E Bernd, Stoll, Monika, Seedorf, Udo, Rothwell, Peter M, Powell, Janet T, Kuivaniemi, Helena, Onundarson, Pall T, Valdimarsson, Einar, Matthiasson, Stefan E, Gudbjartsson, Daniel F, Thorgeirsson, Guðmundur, Quyyumi, Arshed A, Watkins, Hugh, Farrall, Martin, Thorsteinsdottir, Unnur, Stefansson, Kari, Helgadottir, Anna, Gretarsdottir, Solveig, Thorleifsson, Gudmar, Holm, Hilma, Patel, Riyaz S, Gudnason, Thorarinn, Jones, Gregory T, van Rij, Andre M, Eapen, Danny J, Baas, Annette F, Tregouet, David-Alexandre, Morange, Pierre-Emmanuel, Emmerich, Joseph, Lindblad, Bengt, Gottsäter, Anders, Kiemeny, Lambertus A, Lindholt, Jes S., Sakalihasan, Natzi, Ferrell, Robert E, Carey, David J, Elmore, James R, Tsao, Philip S, Grarup, Niels, Jørgensen, Torben, Witte, Daniel R, Hansen, Torben, Pedersen, Oluf, Pola, Roberto, Gaetani, Eleonora, Magnadottir, Hulda B, Wijmenga, Cisca, Tromp, Gerard, Ronkainen, Antti, Ruigrok, Ynte M, Blankensteijn, Jan D, Mueller, Thomas, Wells, Philip S, Corral, Javier, Soria, Jose Manuel, Souto, Juan Carlos, Peden, John F, Jalilzadeh, Shapour, Mayosi, Bongani M, Keavney, Bernard, Strawbridge, Rona J, Sabater-Lleal, Maria, Gertow, Karl, Baldassarre, Damiano, Nyyssönen, Kristiina, Rauramaa, Rainer, Smit, Andries J, Mannarino, Elmo, Giral, Philippe, Tremoli, Elena, de Faire, Ulf, Humphries, Steve E, Hamsten, Anders, Haraldsdottir, Vilhelmina, Olafsson, Isleifur, Magnusson, Magnus K, Samani, Nilesh J, Levey, Allan I, Markus, Hugh S, Kostulas, Konstantinos, Dichgans, Martin, Berger, Klaus, Kuhlenbäumer, Gregor, Ringelstein, E Bernd, Stoll, Monika, Seedorf, Udo, Rothwell, Peter M, Powell, Janet T, Kuivaniemi, Helena, Onundarson, Pall T, Valdimarsson, Einar, Matthiasson, Stefan E, Gudbjartsson, Daniel F, Thorgeirsson, Guðmundur, Quyyumi, Arshed A, Watkins, Hugh, Farrall, Martin, Thorsteinsdottir, Unnur, and Stefansson, Kari

Abstract

The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components.

Published
2012

9. Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

Author

Helgadottir, Anna, primary, Gretarsdottir, Solveig, additional, Thorleifsson, Gudmar, additional, Holm, Hilma, additional, Patel, Riyaz S., additional, Gudnason, Thorarinn, additional, Jones, Gregory T., additional, van Rij, Andre M., additional, Eapen, Danny J., additional, Baas, Annette F., additional, Tregouet, David-Alexandre, additional, Morange, Pierre-Emmanuel, additional, Emmerich, Joseph, additional, Lindblad, Bengt, additional, Gottsäter, Anders, additional, Kiemeny, Lambertus A., additional, Lindholt, Jes S., additional, Sakalihasan, Natzi, additional, Ferrell, Robert E., additional, Carey, David J., additional, Elmore, James R., additional, Tsao, Philip S., additional, Grarup, Niels, additional, Jørgensen, Torben, additional, Witte, Daniel R., additional, Hansen, Torben, additional, Pedersen, Oluf, additional, Pola, Roberto, additional, Gaetani, Eleonora, additional, Magnadottir, Hulda B., additional, Wijmenga, Cisca, additional, Tromp, Gerard, additional, Ronkainen, Antti, additional, Ruigrok, Ynte M., additional, Blankensteijn, Jan D., additional, Mueller, Thomas, additional, Wells, Philip S., additional, Corral, Javier, additional, Soria, Jose Manuel, additional, Souto, Juan Carlos, additional, Peden, John F., additional, Jalilzadeh, Shapour, additional, Mayosi, Bongani M., additional, Keavney, Bernard, additional, Strawbridge, Rona J., additional, Sabater-Lleal, Maria, additional, Gertow, Karl, additional, Baldassarre, Damiano, additional, Nyyssönen, Kristiina, additional, Rauramaa, Rainer, additional, Smit, Andries J., additional, Mannarino, Elmo, additional, Giral, Philippe, additional, Tremoli, Elena, additional, de Faire, Ulf, additional, Humphries, Steve E., additional, Hamsten, Anders, additional, Haraldsdottir, Vilhelmina, additional, Olafsson, Isleifur, additional, Magnusson, Magnus K., additional, Samani, Nilesh J., additional, Levey, Allan I., additional, Markus, Hugh S., additional, Kostulas, Konstantinos, additional, Dichgans, Martin, additional, Berger, Klaus, additional, Kuhlenbäumer, Gregor, additional, Ringelstein, E. Bernd, additional, Stoll, Monika, additional, Seedorf, Udo, additional, Rothwell, Peter M., additional, Powell, Janet T., additional, Kuivaniemi, Helena, additional, Onundarson, Pall T., additional, Valdimarsson, Einar, additional, Matthiasson, Stefan E., additional, Gudbjartsson, Daniel F., additional, Thorgeirsson, Guðmundur, additional, Quyyumi, Arshed A., additional, Watkins, Hugh, additional, Farrall, Martin, additional, Thorsteinsdottir, Unnur, additional, and Stefansson, Kari, additional

Published
2012
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10. A rare variant in MYH6 is associated with high risk of sick sinus syndrome.

Author

Holm, Hilma, Gudbjartsson, Daniel F., Sulem, Patrick, Masson, Gisli, Helgadottir, Hafdis Th, Zanon, Carlo, Magnusson, Olafur Th, Helgason, Agnar, Saemundsdottir, Jona, Gylfason, Arnaldur, Stefansdottir, Hrafnhildur, Gretarsdottir, Solveig, Matthiasson, Stefan E., Thorgeirsson, Guðmundur, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Stefansson, Hreinn, Werge, Thomas, Rafnar, Thorunn, and Kiemeney, Lambertus A.

Subjects
SICK sinus syndrome, MYOSIN, BRADYCARDIA, TACHYARRHYTHMIAS, ATRIAL fibrillation, ION channels
Abstract

Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 × 10?29. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant. [ABSTRACT FROM AUTHOR]

Published
2011
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11. Vaccinia Virus Complement Control Protein Diminishes Formation of Atherosclerotic Lesions: Complement Is Centrally Involved in Atherosclerotic Disease.

Author

THORBJORNSDOTTIR, PERLA, KOLKA, RAGNHILDUR, GUNNARSSON, EGGERT, BAMBIR, SLAVKO H., THORGEIRSSON, GUÐMUNDUR, KOTWAL, GIRISH J., and ARASON, GUÐMUNDUR J.

Subjects
VIRUS diseases in cattle, VACCINIA, PROTEINS, LABORATORY rabbits, PATHOLOGY
Abstract

Complement is known to be activated in atherosclerotic lesions, but the importance of this event in disease pathology is a matter of debate. Studies of rabbits fed a high-fat diet have indicated complement activation as a rate-limiting step, whereas results from genetically modified mouse strains (ApoE-/- or LDLR-/-) have failed to support this finding. To resolve whether this reflects differences between species or between genetically driven and diet-induced disease, we studied the effect of a complement inhibitor, vaccinia virus complement control protein (VCP), on C57BL/6 mice, the background strain of ApoE-/- and LDLR-/- mice. Atherosclerosis was induced by a high-fat diet, and VCP (20 mg/kg) was injected once per week after the eighth week. Fatty streak development was monitored at 15 weeks by microscopic examination of oil red-O-stained sections from the root of the aorta. VCP injections led to significant (50%) reduction of lesion size (P = 0.004). Lesions were marked by gradual accumulation of lipids and macrophages but did not develop beyond the fatty streak stage. VCP activity disappeared from serum in 4 days, and the possibility therefore exists that a higher level of protection may be achieved by more frequent injections. We conclude that the development of fatty streaks in diet-induced atherosclerotic disease can be significantly retarded by prophylactic treatment with a complement inhibitor. These results support previous findings from complement-deficient rabbits and suggest that the pathogenesis of atherosclerosis in diet-induced disease differs from that induced by major defects in lipid metabolism. [ABSTRACT FROM AUTHOR]

Published
2005
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13. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author

Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjörnsson, Garðar, Fatemifar, Ghazaleh, Hedman, Åsa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Ärnlöv, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engström, Gunnar, Esko, Tõnu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gutmann, Rebecca, Haggerty, Christopher M, Van Der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, März, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Regeneron Genetics Center, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, Van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, Stott, David J, Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G, Veluchamy, Abirami, Völker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Waterworth, Dawn, Weeke, Peter E, Weiss, Raul, Wiggins, Kerri L, Xing, Heming, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J, McMurray, John JV, Yang, Jian, Visscher, Peter M, Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A, Sattar, Naveed, Holmes, Michael V, Cappola, Thomas P, Asselbergs, Folkert W, Hingorani, Aroon D, Kuchenbaecker, Karoline, Ellinor, Patrick T, Lang, Chim C, Stefansson, Kari, Smith, J Gustav, Vasan, Ramachandran S, Swerdlow, Daniel I, and Lumbers, R Thomas

Subjects
2. Zero hunger, Cyclin-Dependent Kinase Inhibitor p21, Heart Failure, Microfilament Proteins, Muscle Proteins, Coronary Artery Disease, Mendelian Randomization Analysis, Ventricular Function, Left, 3. Good health, Risk Factors, Case-Control Studies, Atrial Fibrillation, Humans, Apoptosis Regulatory Proteins, Cardiomyopathies, Carrier Proteins, Adaptor Proteins, Signal Transducing, Genome-Wide Association Study
Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

14. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author

Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjörnsson, Garðar, Fatemifar, Ghazaleh, Hedman, Åsa K., Wilk, Jemma B., Morley, Michael P., Chaffin, Mark D., Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G., Ärnlöv, Johan, Backman, Joshua D., Biggs, Mary L., Bloom, Heather L., Brandimarto, Jeffrey, Brown, Michael R., Buckbinder, Leonard, Carey, David J., Chasman, Daniel I., Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P., Delgado, Graciela E., Denaxas, Spiros, Doney, Alexander S., Dörr, Marcus, Dudley, Samuel C., Dunn, Michael E., Engström, Gunnar, Esko, Tõnu, Felix, Stephan B., Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S., Gross, Stefan, Guðbjartsson, Daníel F., Gutmann, Rebecca, Haggerty, Christopher M., Van Der Harst, Pim, Hyde, Craig L., Ingelsson, Erik, Jukema, J. Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E., Køber, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M., London, Barry, Lotta, Luca A., Lovering, Ruth C., Luan, Jian’an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B., März, Winfried, Melander, Olle, Mordi, Ify R., Morgan, Thomas, Morris, Andrew D., Morris, Andrew P., Morrison, Alanna C., Nagle, Michael W., Nelson, Christopher P., Niessner, Alexander, Niiranen, Teemu, O’Donoghue, Michelle L., Owens, Anjali T., Palmer, Colin N. A., Parry, Helen M., Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M., Rice, Kenneth M., Ridker, Paul M., Romaine, Simon P. R., Rotter, Jerome I., Salo, Perttu, Salomaa, Veikko, Van Setten, Jessica, Shalaby, Alaa A., Smelser, Diane T., Smith, Nicholas L., Stender, Steen, Stott, David J., Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D., Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G., Veluchamy, Abirami, Völker, Uwe, Voors, Adriaan A., Wang, Xiaosong, Wareham, Nicholas J., Waterworth, Dawn, Weeke, Peter E., Weiss, Raul, Wiggins, Kerri L., Xing, Heming, Yerges-Armstrong, Laura M., Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J., McMurray, John J. V., Yang, Jian, Visscher, Peter M., Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A., Sattar, Naveed, Holmes, Michael V., Cappola, Thomas P., Asselbergs, Folkert W., Hingorani, Aroon D., Kuchenbaecker, Karoline, Ellinor, Patrick T., Lang, Chim C., Stefansson, Kari, Smith, J. Gustav, Vasan, Ramachandran S., Swerdlow, Daniel I., Lumbers, R. Thomas, Abecasis, Goncalo, Backman, Joshua, Bai, Xiaodong, Balasubramanian, Suganthi, Banerjee, Nilanjana, Baras, Aris, Barnard, Leland, Beechert, Christina, Blumenfeld, Andrew, Cantor, Michael, Chai, Yating, Coppola, Giovanni, Damask, Amy, Dewey, Frederick, Economides, Aris, Eom, Gisu, Forsythe, Caitlin, Fuller, Erin D., Gu, Zhenhua, Gurski, Lauren, Guzzardo, Paloma M., Habegger, Lukas, Hahn, Young, Hawes, Alicia, Van Hout, Cristopher, Jones, Marcus B., Khalid, Shareef, Lattari, Michael, Li, Alexander, Lin, Nan, Liu, Daren, Lopez, Alexander, Manoochehri, Kia, Marchini, Jonathan, Marcketta, Anthony, Maxwell, Evan K., McCarthy, Shane, Mitnaul, Lyndon J., O’Dushlaine, Colm, Overton, John D., Padilla, Maria Sotiropoulos, Paulding, Charles, Penn, John, Pradhan, Manasi, Reid, Jeffrey G., Schleicher, Thomas D., Schurmann, Claudia, Shuldiner, Alan, Staples, Jeffrey C., Sun, Dylan, Toledo, Karina, Ulloa, Ricardo H., Widom, Louis, Wolf, Sarah E., Yadav, Ashish, and Ye, Bin

Subjects
2. Zero hunger, 631/443/592/2727, 631/208/205/2138, 692/699/75/230, 45/43, article, 692/308/174, 3. Good health
Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

15. The genomics of heart failure: design and rationale of the HERMES consortium

Author

Lumbers, R. Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I., Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V., Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G., Asselin, Geraldine, Backman, Joshua D., Biggs, Mary L., Bloom, Heather L., Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R., Brunner‐La Rocca, Hans‐Peter, Carey, David J., Chaffin, Mark D., Chasman, Daniel I., Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H., Chutkow, William, Cleland, John G.F., Cook, James P., De Denus, Simon, Dehghan, Abbas, Delgado, Graciela E., Denaxas, Spiros, Doney, Alexander S., Dörr, Marcus, Dudley, Samuel C., Engström, Gunnar, Esko, Tõnu, Fatemifar, Ghazaleh, Felix, Stephan B., Finan, Chris, Ford, Ian, Fougerousse, Francoise, Fouodjio, René, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S., Gross, Stefan, Guðbjartsson, Daníel F., Gui, Hongsheng, Gutmann, Rebecca, Haggerty, Christopher M., Van Der Harst, Pim, Hedman, Åsa K., Helgadottir, Anna, Hillege, Hans, Hyde, Craig L., Jacob, Jaison, Jukema, J. Wouter, Kamanu, Frederick, Kardys, Isabella, Kavousi, Maryam, Khaw, Kay‐Tee, Kleber, Marcus E., Køber, Lars, Koekemoer, Andrea, Kraus, Bill, Kuchenbaecker, Karoline, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M., London, Barry, Lotta, Luca A., Lovering, Ruth C., Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Mann, Douglas, Margulies, Kenneth B., Marston, Nicholas A., März, Winfried, McMurray, John J.V., Melander, Olle, Melloni, Giorgio, Mordi, Ify R., Morley, Michael P., Morris, Andrew D., Morris, Andrew P., Morrison, Alanna C., Nagle, Michael W., Nelson, Christopher P., Newton‐Cheh, Christopher, Niessner, Alexander, Niiranen, Teemu, Nowak, Christoph, O'Donoghue, Michelle L., Owens, Anjali T., Palmer, Colin N.A., Paré, Guillaume, Perola, Markus, Perreault, Louis‐Philippe Lemieux, Portilla‐Fernandez, Eliana, Psaty, Bruce M., Rice, Kenneth M., Ridker, Paul M., Romaine, Simon P.R., Roselli, Carolina, Rotter, Jerome I., Ruff, Christian T., Sabatine, Marc S., Salo, Perttu, Salomaa, Veikko, Van Setten, Jessica, Shalaby, Alaa A., Smelser, Diane T., Smith, Nicholas L., Stefansson, Kari, Stender, Steen, Stott, David J., Sveinbjörnsson, Garðar, Tammesoo, Mari‐Liis, Tardif, Jean‐Claude, Taylor, Kent D., Teder‐Laving, Maris, Teumer, Alexander, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Torp‐Pedersen, Christian, Trompet, Stella, Tuckwell, Danny, Tyl, Benoit, Uitterlinden, Andre G., Vaura, Felix, Veluchamy, Abirami, Visscher, Peter M., Völker, Uwe, Voors, Adriaan A., Wang, Xiaosong, Wareham, Nicholas J., Weeke, Peter E., Weiss, Raul, White, Harvey D., Wiggins, Kerri L., Xing, Heming, Yang, Jian, Yang, Yifan, Yerges‐Armstrong, Laura M., Yu, Bing, Zannad, Faiez, Zhao, Faye, Regeneron Genetics Center, Wilk, Jemma B., Holm, Hilma, Sattar, Naveed, Lubitz, Steven A., Lanfear, David E., Shah, Svati, Dunn, Michael E., Wells, Quinn S., Asselbergs, Folkert W., Hingorani, Aroon D., Dubé, Marie‐Pierre, Samani, Nilesh J., Lang, Chim C., Cappola, Thomas P., Ellinor, Patrick T., Vasan, Ramachandran S., and Smith, J. Gustav

Subjects
Study Design, Cardiomyopathy, FOS: Biological sciences, Study Designs, Genetics, Heart failure, Biomarkers, 3. Good health, Association studies
Abstract

Funder: Knut and Alice Wallenberg Foundation; Id: http://dx.doi.org/10.13039/501100004063, Funder: Swedish National Health Service, Funder: Skåne University Hospital; Id: http://dx.doi.org/10.13039/501100011077, Funder: Crafoord Foundation; Id: http://dx.doi.org/10.13039/501100003173, Funder: Department of Medicine, Boston University School of Medicine; Id: http://dx.doi.org/10.13039/100008748, Funder: Evans Medical Foundation; Id: http://dx.doi.org/10.13039/100015927, Funder: National Heart, Lung, and Blood Institute; Id: http://dx.doi.org/10.13039/100000050, Funder: British Heart Foundation Cardiovascular Biomedicine, Funder: NIHR UCLH Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012317, Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome‐wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow‐up following heart failure diagnosis ranged from 2 to 116 months. Forty‐nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34–90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low‐frequency variants (allele frequency 0.01–0.05) at P < 5 × 10−8 under an additive genetic model. Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

16. The genomics of heart failure: design and rationale of the HERMES consortium

Author

Lumbers, R Thomas, Shah, Sonia, Lin, Honghuang, Czuba, Tomasz, Henry, Albert, Swerdlow, Daniel I, Mälarstig, Anders, Andersson, Charlotte, Verweij, Niek, Holmes, Michael V, Ärnlöv, Johan, Svensson, Per, Hemingway, Harry, Sallah, Neneh, Almgren, Peter, Aragam, Krishna G, Asselin, Geraldine, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Boersma, Eric, Brandimarto, Jeffrey, Brown, Michael R, Brunner-La Rocca, Hans-Peter, Carey, David J, Chaffin, Mark D, Chasman, Daniel I, Chazara, Olympe, Chen, Xing, Chen, Xu, Chung, Jonathan H, Chutkow, William, Cleland, John GF, Cook, James P, De Denus, Simon, Dehghan, Abbas, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Engström, Gunnar, Esko, Tõnu, Fatemifar, Ghazaleh, Felix, Stephan B, Finan, Chris, Ford, Ian, Fougerousse, Francoise, Fouodjio, René, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gui, Hongsheng, Gutmann, Rebecca, Haggerty, Christopher M, Van Der Harst, Pim, Hedman, Åsa K, Helgadottir, Anna, Hillege, Hans, Hyde, Craig L, Jacob, Jaison, Jukema, J Wouter, Kamanu, Frederick, Kardys, Isabella, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Kraus, Bill, Kuchenbaecker, Karoline, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Mann, Douglas, Margulies, Kenneth B, Marston, Nicholas A, März, Winfried, McMurray, John JV, Melander, Olle, Melloni, Giorgio, Mordi, Ify R, Morley, Michael P, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Newton-Cheh, Christopher, Niessner, Alexander, Niiranen, Teemu, Nowak, Christoph, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Paré, Guillaume, Perola, Markus, Perreault, Louis-Philippe Lemieux, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Roselli, Carolina, Rotter, Jerome I, Ruff, Christian T, Sabatine, Marc S, Salo, Perttu, Salomaa, Veikko, Van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stefansson, Kari, Stender, Steen, Stott, David J, Sveinbjörnsson, Garðar, Tammesoo, Mari-Liis, Tardif, Jean-Claude, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tuckwell, Danny, Tyl, Benoit, Uitterlinden, Andre G, Vaura, Felix, Veluchamy, Abirami, Visscher, Peter M, Völker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Weeke, Peter E, Weiss, Raul, White, Harvey D, Wiggins, Kerri L, Xing, Heming, Yang, Jian, Yang, Yifan, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Faye, Regeneron Genetics Center, Wilk, Jemma B, Holm, Hilma, Sattar, Naveed, Lubitz, Steven A, Lanfear, David E, Shah, Svati, Dunn, Michael E, Wells, Quinn S, Asselbergs, Folkert W, Hingorani, Aroon D, Dubé, Marie-Pierre, Samani, Nilesh J, Lang, Chim C, Cappola, Thomas P, Ellinor, Patrick T, Vasan, Ramachandran S, and Smith, J Gustav

Subjects
Aged, 80 and over, Heart Failure, Male, Cardiomyopathy, Genomics, Middle Aged, 16. Peace & justice, Prognosis, 3. Good health, FOS: Biological sciences, Genetics, Humans, Female, Biomarkers, Association studies, Aged, Genome-Wide Association Study
Abstract

AIMS: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure. METHODS AND RESULTS: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10-8 under an additive genetic model. CONCLUSIONS: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

17. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author

Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjörnsson, Garðar, Fatemifar, Ghazaleh, Hedman, Åsa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Ärnlöv, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engström, Gunnar, Esko, Tõnu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gutmann, Rebecca, Haggerty, Christopher M, Van Der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, März, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin N A, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon P R, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, Van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, Stott, David J, Svensson, Per, Tammesoo, Mari-Liis, Taylor, Kent D, Teder-Laving, Maris, Teumer, Alexander, Thorgeirsson, Guðmundur, Thorsteinsdottir, Unnur, Torp-Pedersen, Christian, Trompet, Stella, Tyl, Benoit, Uitterlinden, Andre G, Veluchamy, Abirami, Völker, Uwe, Voors, Adriaan A, Wang, Xiaosong, Wareham, Nicholas J, Waterworth, Dawn, Weeke, Peter E, Weiss, Raul, Wiggins, Kerri L, Xing, Heming, Yerges-Armstrong, Laura M, Yu, Bing, Zannad, Faiez, Zhao, Jing Hua, Hemingway, Harry, Samani, Nilesh J, McMurray, John J V, Yang, Jian, Visscher, Peter M, Newton-Cheh, Christopher, Malarstig, Anders, Holm, Hilma, Lubitz, Steven A, Sattar, Naveed, Holmes, Michael V, Cappola, Thomas P, Asselbergs, Folkert W, Hingorani, Aroon D, Kuchenbaecker, Karoline, Ellinor, Patrick T, Lang, Chim C, Stefansson, Kari, Smith, J Gustav, Vasan, Ramachandran S, Swerdlow, Daniel I, and Lumbers, R Thomas

Subjects
2. Zero hunger, 3. Good health
Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

20. The genomics of heart failure: design and rationale of the HERMES consortium.

Author

Lumbers RT, Shah S, Lin H, Czuba T, Henry A, Swerdlow DI, Mälarstig A, Andersson C, Verweij N, Holmes MV, Ärnlöv J, Svensson P, Hemingway H, Sallah N, Almgren P, Aragam KG, Asselin G, Backman JD, Biggs ML, Bloom HL, Boersma E, Brandimarto J, Brown MR, Brunner-La Rocca HP, Carey DJ, Chaffin MD, Chasman DI, Chazara O, Chen X, Chen X, Chung JH, Chutkow W, Cleland JGF, Cook JP, de Denus S, Dehghan A, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Engström G, Esko T, Fatemifar G, Felix SB, Finan C, Ford I, Fougerousse F, Fouodjio R, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gui H, Gutmann R, Haggerty CM, van der Harst P, Hedman ÅK, Helgadottir A, Hillege H, Hyde CL, Jacob J, Jukema JW, Kamanu F, Kardys I, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Kraus B, Kuchenbaecker K, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Mann D, Margulies KB, Marston NA, März W, McMurray JJV, Melander O, Melloni G, Mordi IR, Morley MP, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Newton-Cheh C, Niessner A, Niiranen T, Nowak C, O'Donoghue ML, Owens AT, Palmer CNA, Paré G, Perola M, Perreault LL, Portilla-Fernandez E, Psaty BM, Rice KM, Ridker PM, Romaine SPR, Roselli C, Rotter JI, Ruff CT, Sabatine MS, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stefansson K, Stender S, Stott DJ, Sveinbjörnsson G, Tammesoo ML, Tardif JC, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tuckwell D, Tyl B, Uitterlinden AG, Vaura F, Veluchamy A, Visscher PM, Völker U, Voors AA, Wang X, Wareham NJ, Weeke PE, Weiss R, White HD, Wiggins KL, Xing H, Yang J, Yang Y, Yerges-Armstrong LM, Yu B, Zannad F, Zhao F, Wilk JB, Holm H, Sattar N, Lubitz SA, Lanfear DE, Shah S, Dunn ME, Wells QS, Asselbergs FW, Hingorani AD, Dubé MP, Samani NJ, Lang CC, Cappola TP, Ellinor PT, Vasan RS, and Smith JG

Subjects
Aged, Aged, 80 and over, Female, Genomics, Humans, Male, Middle Aged, Prognosis, Genome-Wide Association Study, Heart Failure genetics
Abstract

Aims: The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure., Methods and Results: The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of ≥1.10 for common variants (allele frequency ≥ 0.05) and ≥1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 × 10 -8 under an additive genetic model., Conclusions: HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Published
2021
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21. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.

Author

Shah S, Henry A, Roselli C, Lin H, Sveinbjörnsson G, Fatemifar G, Hedman ÅK, Wilk JB, Morley MP, Chaffin MD, Helgadottir A, Verweij N, Dehghan A, Almgren P, Andersson C, Aragam KG, Ärnlöv J, Backman JD, Biggs ML, Bloom HL, Brandimarto J, Brown MR, Buckbinder L, Carey DJ, Chasman DI, Chen X, Chen X, Chung J, Chutkow W, Cook JP, Delgado GE, Denaxas S, Doney AS, Dörr M, Dudley SC, Dunn ME, Engström G, Esko T, Felix SB, Finan C, Ford I, Ghanbari M, Ghasemi S, Giedraitis V, Giulianini F, Gottdiener JS, Gross S, Guðbjartsson DF, Gutmann R, Haggerty CM, van der Harst P, Hyde CL, Ingelsson E, Jukema JW, Kavousi M, Khaw KT, Kleber ME, Køber L, Koekemoer A, Langenberg C, Lind L, Lindgren CM, London B, Lotta LA, Lovering RC, Luan J, Magnusson P, Mahajan A, Margulies KB, März W, Melander O, Mordi IR, Morgan T, Morris AD, Morris AP, Morrison AC, Nagle MW, Nelson CP, Niessner A, Niiranen T, O'Donoghue ML, Owens AT, Palmer CNA, Parry HM, Perola M, Portilla-Fernandez E, Psaty BM, Rice KM, Ridker PM, Romaine SPR, Rotter JI, Salo P, Salomaa V, van Setten J, Shalaby AA, Smelser DT, Smith NL, Stender S, Stott DJ, Svensson P, Tammesoo ML, Taylor KD, Teder-Laving M, Teumer A, Thorgeirsson G, Thorsteinsdottir U, Torp-Pedersen C, Trompet S, Tyl B, Uitterlinden AG, Veluchamy A, Völker U, Voors AA, Wang X, Wareham NJ, Waterworth D, Weeke PE, Weiss R, Wiggins KL, Xing H, Yerges-Armstrong LM, Yu B, Zannad F, Zhao JH, Hemingway H, Samani NJ, McMurray JJV, Yang J, Visscher PM, Newton-Cheh C, Malarstig A, Holm H, Lubitz SA, Sattar N, Holmes MV, Cappola TP, Asselbergs FW, Hingorani AD, Kuchenbaecker K, Ellinor PT, Lang CC, Stefansson K, Smith JG, Vasan RS, Swerdlow DI, and Lumbers RT

Subjects
Adaptor Proteins, Signal Transducing genetics, Apoptosis Regulatory Proteins genetics, Cardiomyopathies pathology, Carrier Proteins genetics, Case-Control Studies, Cyclin-Dependent Kinase Inhibitor p21 genetics, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Microfilament Proteins genetics, Muscle Proteins genetics, Risk Factors, Atrial Fibrillation genetics, Cardiomyopathies genetics, Coronary Artery Disease genetics, Heart Failure genetics, Heart Failure pathology, Ventricular Function, Left genetics
Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Published
2020
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22. [Review on coronary artery disease--Part II: medical treatment, percutaneous interventions and myocardial revascularization].

Author

Gudbjartsson T, Andersen K, Danielsen R, Geirsson A, and Thorgeirsson G

Subjects
Coronary Angiography, Coronary Artery Disease diagnosis, Coronary Artery Disease surgery, Humans, Iceland, Stents, Treatment Outcome, Coronary Artery Bypass adverse effects, Coronary Artery Disease therapy, Percutaneous Coronary Intervention adverse effects, Percutaneous Coronary Intervention instrumentation
Abstract

This article is the second of two review articles on coronary artery disease. The focus is on treatment with coverage of medical treatment, intravascular interventions and surgical therapy. The review is aimed at a wide readership of physicians and other health care providers but also at students of various health sciences. Current literature is reviewed with special focus on recent Icelandic studies.

Published
2015
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23. [Pulmonary embolism at Landspítali, the National University Hospital of Iceland 2005-2007 - incidence, clinical manifestations, risk factors and outcome].

Author

Jonsson KO, Agnarsson UT, Danielsen R, and Thorgeirsson G

Subjects
Aged, Aged, 80 and over, Anticoagulants therapeutic use, Dyspnea etiology, Female, Hospital Mortality, Humans, Iceland epidemiology, Incidence, Male, Middle Aged, Predictive Value of Tests, Pulmonary Embolism diagnosis, Pulmonary Embolism mortality, Pulmonary Embolism therapy, Retrospective Studies, Risk Factors, Thrombectomy, Thrombolytic Therapy, Time Factors, Tomography, X-Ray Computed, Treatment Outcome, Vena Cava Filters, Hospitals, University statistics & numerical data, Inpatients statistics & numerical data, Pulmonary Embolism epidemiology
Abstract

Introduction: Pulmonary embolism is a serious disease and common among hospitalized patients. The incidence of pulmonary embolism in Iceland is largely unknown. The purpose of this study was to evaluate the incidence, clinical presentation, risk factors and outcome among patients diagnosed with pulmonary embolism at Landspítali, The National University Hospital of Iceland., Material and Methods: A retrospective analysis of medical records of patients diagnosed with the ICD-10 diagnosis I26 (Pulmonary embolism) between 2005-2007 was carried out. Data were retrieved on age, clinical manifestations, treatment, risk factors, diagnostic procedures and outcome., Results: The total number of patients was 312 and the in-hospital incidence was 5 per 1.000. Thirty day mortality was 9.9% (95% CI 6.6-13.3). Dyspnea was the most common symptom (81%) and diagnosis was most often established by computed tomography of the pulmonary vasculature (88,8%). Anticoagulation was by far the most common management (96%) but thrombolysis, thrombectomy or use of inferior vena cava filters were very rare. The frequency of atrial fibrillation was significantly higher in patients with pulmonary hypertension by echocardiography than without, 32.4% and 9.7%, respectively (p= 0.026). Thirty day mortality was significantly higher in women than in men (13.2% versus 6.5%, p=0.049), and in patients with no classic symptoms of pulmonary embolism at diagnosis (36.4% versus 8.1%, p=0.012)., Discussion: The hospital incidence of pulmonary embolism, 5/1000 patients, at Landspítali The National University Hospital of Iceland is higher than found in similar studies in many other countries. Mortality, while similar, has fallen markedly during the past 40 years.

Published
2013
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