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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
- Source :
- Nature Communications, 11(1). NATURE PUBLISHING GROUP, Nature Communications, Nature Communications, 11(1):163. Nature Publishing Group, Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020), Shah, S, Henry, A, Roselli, C, Lin, H, Sveinbjörnsson, G, Fatemifar, G, Hedman, Å K, Wilk, J B, Morley, M P, Chaffin, M D, Helgadottir, A, Verweij, N, Dehghan, A, Almgren, P, Andersson, C, Aragam, K G, Ärnlöv, J, Backman, J D, Biggs, M L, Bloom, H L, Brandimarto, J, Brown, M R, Buckbinder, L, Carey, D J, Chasman, D I, Chen, X, Chen, X, Chung, J, Chutkow, W, Cook, J P, Delgado, G E, Denaxas, S, Doney, A S, Dörr, M, Dudley, S C, Dunn, M E, Engström, G, Esko, T, Felix, S B, Finan, C, Ford, I, Ghanbari, M, Ghasemi, S, Giedraitis, V, Giulianini, F, Gottdiener, J S, Gross, S, Guðbjartsson, D F, Gutmann, R, Haggerty, C M, van der Harst, P, Hyde, C L, Ingelsson, E, Jukema, J W, Kavousi, M, Khaw, K-T, Kleber, M E, Køber, L, Koekemoer, A, Langenberg, C, Lind, L, Lindgren, C M, London, B, Lotta, L A, Lovering, R C, Luan, J, Magnusson, P, Mahajan, A, Margulies, K B, März, W, Melander, O, Mordi, I R, Morgan, T, Morris, A D, Morris, A P, Morrison, A C, Nagle, M W, Nelson, C P, Niessner, A, Niiranen, T, O’Donoghue, M L, Owens, A T, Palmer, C N A, Parry, H M, Perola, M, Portilla-Fernandez, E, Psaty, B M, Abecasis, G, Backman, J, Bai, X, Balasubramanian, S, Banerjee, N, Baras, A, Barnard, L, Beechert, C, Blumenfeld, A, Cantor, M, Chai, Y, Coppola, G, Damask, A, Dewey, F, Economides, A, Eom, G, Forsythe, C, Fuller, E D, Gu, Z, Gurski, L, Guzzardo, P M, Habegger, L, Hahn, Y, Hawes, A, van Hout, C, Jones, M B, Khalid, S, Lattari, M, Li, A, Lin, N, Liu, D, Lopez, A, Manoochehri, K, Marchini, J, Marcketta, A, Maxwell, E K, McCarthy, S, Mitnaul, L J, O’Dushlaine, C, Overton, J D, Padilla, M S, Paulding, C, Penn, J, Pradhan, M, Reid, J G, Schleicher, T D, Schurmann, C, Shuldiner, A, Staples, J C, Sun, D, Toledo, K, Ulloa, R H, Widom, L, Wolf, S E, Yadav, A, Ye, B, Rice, K M, Ridker, P M, Romaine, S P R, Rotter, J I, Salo, P, Salomaa, V, van Setten, J, Shalaby, A A, Smelser, D T, Smith, N L, Stender, S, Stott, D J, Svensson, P, Tammesoo, M-L, Taylor, K D, Teder-Laving, M, Teumer, A, Thorgeirsson, G, Thorsteinsdottir, U, Torp-Pedersen, C, Trompet, S, Tyl, B, Uitterlinden, A G, Veluchamy, A, Völker, U, Voors, A A, Wang, X, Wareham, N J, Waterworth, D, Weeke, P E, Weiss, R, Wiggins, K L, Xing, H, Yerges-Armstrong, L M, Yu, B, Zannad, F, Zhao, J H, Hemingway, H, Samani, N J, McMurray, J J V, Yang, J, Visscher, P M, Newton-Cheh, C, Malarstig, A, Holm, H, Lubitz, S A, Sattar, N, Holmes, M V, Cappola, T P, Asselbergs, F W, Hingorani, A D, Kuchenbaecker, K, Ellinor, P T, Lang, C C, Stefansson, K, Smith, J G, Vasan, R S, Swerdlow, D I & Lumbers, R T 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, no. 1, 163 . https://doi.org/10.1038/s41467-019-13690-5, 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, no. 1, pp. 163 . https://doi.org/10.1038/s41467-019-13690-5, Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.163. ⟨10.1038/s41467-019-13690-5⟩, Shah, S, Henry, A, Roselli, C, Lin, H, Sveinbjörnsson, G, Fatemifar, G, Hedman, Å K, Wilk, J B, Morley, M P, Chaffin, M D, Helgadottir, A, Verweij, N, Dehghan, A, Almgren, P, Andersson, C, Aragam, K G, Ärnlöv, J, Backman, J D, Biggs, M L, Bloom, H L, Brandimarto, J, Brown, M R, Buckbinder, L, Carey, D J, Chasman, D I, Chen, X, Chen, X, Chung, J, Chutkow, W, Cook, J P, Delgado, G E, Denaxas, S, Doney, A S, Dörr, M, Dudley, S C, Dunn, M E, Engström, G, Esko, T, Felix, S B, Finan, C, Ford, I, Ghanbari, M, Ghasemi, S, Morris, A P, Morris, A D, Nelson, C P, Smith, N L, Zhao, J H, Yang, J & Holmes, M V 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, no. 1, pp. 163 . https://doi.org/10.1038/s41467-019-13690-5, Shah, S, Henry, A, Roselli, C, Lin, H, Sveinbjörnsson, G, Fatemifar, G, Hedman, Å K, Wilk, J B, Morley, M P, Chaffin, M D, Helgadottir, A, Verweij, N, Dehghan, A, Almgren, P, Andersson, C, Aragam, K G, Ärnlöv, J, Backman, J D, Biggs, M L, Bloom, H L, Brandimarto, J, Brown, M R, Buckbinder, L, Carey, D J, Chasman, D I, Chen, X, Chen, X, Chung, J, Chutkow, W, Cook, J P, Delgado, G E, Denaxas, S, Doney, A S, Dörr, M, Dudley, S C, Dunn, M E, Engström, G, Esko, T, Felix, S B, Finan, C, Ford, I, Ghanbari, M, Ghasemi, S, Giedraitis, V, Giulianini, F, Køber, L, Regeneron Genetics Center, Stender, S, Torp-Pedersen, C, Weeke, P E, Vasan, R S, Swerdlow, D I & Lumbers, R T 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, 163 . https://doi.org/10.1038/s41467-019-13690-5
- Publication Year :
- 2020
- Publisher :
- Springer Nature, 2020.
-
Abstract
- Publisher's version (útgefin grein)<br />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.<br />We acknowledge the contribution from the EchoGen Consortium.
- Subjects :
- 0301 basic medicine
Dánartíðni
Epidemiology
LOCI
45/43
General Physics and Astronomy
Muscle Proteins
Genome-wide association study
Disease
Coronary Artery Disease
030204 cardiovascular system & hematology
Bioinformatics
Genome-wide association studies
DISEASE
Ventricular Function, Left
Coronary artery disease
0302 clinical medicine
Risk Factors
Atrial Fibrillation
IMPUTATION
Medicine
Blóðrásarsjúkdómar
692/308/174
lcsh:Science
2. Zero hunger
RISK
Multidisciplinary
Microfilament Proteins
article
Atrial fibrillation
Mendelian Randomization Analysis
CATALOG
3. Good health
OBESITY
Erfðarannsóknir
Cardiomyopathies
Medical Genetics
Cyclin-Dependent Kinase Inhibitor p21
Science
631/208/205/2138
Heart failure
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
631/443/592/2727
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
RESOURCE
Humans
Mortality
METAANALYSIS
Genetic association
Medicinsk genetik
Adaptor Proteins, Signal Transducing
Heart Failure
HYPERTENSION
business.industry
Case-control study
Klinisk medicin
692/699/75/230
General Chemistry
Cardiovascular genetics
medicine.disease
R1
030104 developmental biology
Case-Control Studies
lcsh:Q
Morbidity
Clinical Medicine
business
Apoptosis Regulatory Proteins
Carrier Proteins
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Nature Communications, 11(1). NATURE PUBLISHING GROUP, Nature Communications, Nature Communications, 11(1):163. Nature Publishing Group, Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020), Shah, S, Henry, A, Roselli, C, Lin, H, Sveinbjörnsson, G, Fatemifar, G, Hedman, Å K, Wilk, J B, Morley, M P, Chaffin, M D, Helgadottir, A, Verweij, N, Dehghan, A, Almgren, P, Andersson, C, Aragam, K G, Ärnlöv, J, Backman, J D, Biggs, M L, Bloom, H L, Brandimarto, J, Brown, M R, Buckbinder, L, Carey, D J, Chasman, D I, Chen, X, Chen, X, Chung, J, Chutkow, W, Cook, J P, Delgado, G E, Denaxas, S, Doney, A S, Dörr, M, Dudley, S C, Dunn, M E, Engström, G, Esko, T, Felix, S B, Finan, C, Ford, I, Ghanbari, M, Ghasemi, S, Giedraitis, V, Giulianini, F, Gottdiener, J S, Gross, S, Guðbjartsson, D F, Gutmann, R, Haggerty, C M, van der Harst, P, Hyde, C L, Ingelsson, E, Jukema, J W, Kavousi, M, Khaw, K-T, Kleber, M E, Køber, L, Koekemoer, A, Langenberg, C, Lind, L, Lindgren, C M, London, B, Lotta, L A, Lovering, R C, Luan, J, Magnusson, P, Mahajan, A, Margulies, K B, März, W, Melander, O, Mordi, I R, Morgan, T, Morris, A D, Morris, A P, Morrison, A C, Nagle, M W, Nelson, C P, Niessner, A, Niiranen, T, O’Donoghue, M L, Owens, A T, Palmer, C N A, Parry, H M, Perola, M, Portilla-Fernandez, E, Psaty, B M, Abecasis, G, Backman, J, Bai, X, Balasubramanian, S, Banerjee, N, Baras, A, Barnard, L, Beechert, C, Blumenfeld, A, Cantor, M, Chai, Y, Coppola, G, Damask, A, Dewey, F, Economides, A, Eom, G, Forsythe, C, Fuller, E D, Gu, Z, Gurski, L, Guzzardo, P M, Habegger, L, Hahn, Y, Hawes, A, van Hout, C, Jones, M B, Khalid, S, Lattari, M, Li, A, Lin, N, Liu, D, Lopez, A, Manoochehri, K, Marchini, J, Marcketta, A, Maxwell, E K, McCarthy, S, Mitnaul, L J, O’Dushlaine, C, Overton, J D, Padilla, M S, Paulding, C, Penn, J, Pradhan, M, Reid, J G, Schleicher, T D, Schurmann, C, Shuldiner, A, Staples, J C, Sun, D, Toledo, K, Ulloa, R H, Widom, L, Wolf, S E, Yadav, A, Ye, B, Rice, K M, Ridker, P M, Romaine, S P R, Rotter, J I, Salo, P, Salomaa, V, van Setten, J, Shalaby, A A, Smelser, D T, Smith, N L, Stender, S, Stott, D J, Svensson, P, Tammesoo, M-L, Taylor, K D, Teder-Laving, M, Teumer, A, Thorgeirsson, G, Thorsteinsdottir, U, Torp-Pedersen, C, Trompet, S, Tyl, B, Uitterlinden, A G, Veluchamy, A, Völker, U, Voors, A A, Wang, X, Wareham, N J, Waterworth, D, Weeke, P E, Weiss, R, Wiggins, K L, Xing, H, Yerges-Armstrong, L M, Yu, B, Zannad, F, Zhao, J H, Hemingway, H, Samani, N J, McMurray, J J V, Yang, J, Visscher, P M, Newton-Cheh, C, Malarstig, A, Holm, H, Lubitz, S A, Sattar, N, Holmes, M V, Cappola, T P, Asselbergs, F W, Hingorani, A D, Kuchenbaecker, K, Ellinor, P T, Lang, C C, Stefansson, K, Smith, J G, Vasan, R S, Swerdlow, D I & Lumbers, R T 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, no. 1, 163 . https://doi.org/10.1038/s41467-019-13690-5, 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, no. 1, pp. 163 . https://doi.org/10.1038/s41467-019-13690-5, Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.163. ⟨10.1038/s41467-019-13690-5⟩, Shah, S, Henry, A, Roselli, C, Lin, H, Sveinbjörnsson, G, Fatemifar, G, Hedman, Å K, Wilk, J B, Morley, M P, Chaffin, M D, Helgadottir, A, Verweij, N, Dehghan, A, Almgren, P, Andersson, C, Aragam, K G, Ärnlöv, J, Backman, J D, Biggs, M L, Bloom, H L, Brandimarto, J, Brown, M R, Buckbinder, L, Carey, D J, Chasman, D I, Chen, X, Chen, X, Chung, J, Chutkow, W, Cook, J P, Delgado, G E, Denaxas, S, Doney, A S, Dörr, M, Dudley, S C, Dunn, M E, Engström, G, Esko, T, Felix, S B, Finan, C, Ford, I, Ghanbari, M, Ghasemi, S, Morris, A P, Morris, A D, Nelson, C P, Smith, N L, Zhao, J H, Yang, J & Holmes, M V 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, no. 1, pp. 163 . https://doi.org/10.1038/s41467-019-13690-5, Shah, S, Henry, A, Roselli, C, Lin, H, Sveinbjörnsson, G, Fatemifar, G, Hedman, Å K, Wilk, J B, Morley, M P, Chaffin, M D, Helgadottir, A, Verweij, N, Dehghan, A, Almgren, P, Andersson, C, Aragam, K G, Ärnlöv, J, Backman, J D, Biggs, M L, Bloom, H L, Brandimarto, J, Brown, M R, Buckbinder, L, Carey, D J, Chasman, D I, Chen, X, Chen, X, Chung, J, Chutkow, W, Cook, J P, Delgado, G E, Denaxas, S, Doney, A S, Dörr, M, Dudley, S C, Dunn, M E, Engström, G, Esko, T, Felix, S B, Finan, C, Ford, I, Ghanbari, M, Ghasemi, S, Giedraitis, V, Giulianini, F, Køber, L, Regeneron Genetics Center, Stender, S, Torp-Pedersen, C, Weeke, P E, Vasan, R S, Swerdlow, D I & Lumbers, R T 2020, ' Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure ', Nature Communications, vol. 11, 163 . https://doi.org/10.1038/s41467-019-13690-5
- Accession number :
- edsair.doi.dedup.....a894b6e7f703eee196676f48718af1b7
- Full Text :
- https://doi.org/10.1038/s41467-019-13690-5