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@article{9967fbe02b224834a80c4e094ef21007,
title = "Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure",
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.",
author = "Sonia Shah and Albert Henry and Carolina Roselli and Honghuang Lin and Gar{\dh}ar Sveinbj{\"o}rnsson and Ghazaleh Fatemifar and Hedman, {{\AA}sa K} and Wilk, {Jemma B} and Morley, {Michael P} and Chaffin, {Mark D} and Anna Helgadottir and Niek Verweij and Abbas Dehghan and Peter Almgren and Charlotte Andersson and Aragam, {Krishna G} and Johan {\"A}rnl{\"o}v and Backman, {Joshua D} and Biggs, {Mary L} and Bloom, {Heather L} and Jeffrey Brandimarto and Brown, {Michael R} and Leonard Buckbinder and Carey, {David J} and Chasman, {Daniel I} and Xing Chen and Xu Chen and Jonathan Chung and William Chutkow and Cook, {James P} and Delgado, {Graciela E} and Spiros Denaxas and Doney, {Alexander S} and Marcus D{\"o}rr and Dudley, {Samuel C} and Dunn, {Michael E} and Gunnar Engstr{\"o}m and T{\~o}nu Esko and Felix, {Stephan B} and Chris Finan and Ian Ford and Mohsen Ghanbari and Sahar Ghasemi and Vilmantas Giedraitis and Franco Giulianini and Gottdiener, {John S} and Lars K{\o}ber and Steen Stender and Christian Torp-Pedersen and Weeke, {Peter E} and {Regeneron Genetics Center}",
year = "2020",
month = jan,
day = "9",
doi = "10.1038/s41467-019-13690-5",
language = "English",
volume = "11",
pages = "163",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
RIS
TY - JOUR
T1 - Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
AU - Shah, Sonia
AU - Henry, Albert
AU - Roselli, Carolina
AU - Lin, Honghuang
AU - Sveinbjörnsson, Garðar
AU - Fatemifar, Ghazaleh
AU - Hedman, Åsa K
AU - Wilk, Jemma B
AU - Morley, Michael P
AU - Chaffin, Mark D
AU - Helgadottir, Anna
AU - Verweij, Niek
AU - Dehghan, Abbas
AU - Almgren, Peter
AU - Andersson, Charlotte
AU - Aragam, Krishna G
AU - Ärnlöv, Johan
AU - Backman, Joshua D
AU - Biggs, Mary L
AU - Bloom, Heather L
AU - Brandimarto, Jeffrey
AU - Brown, Michael R
AU - Buckbinder, Leonard
AU - Carey, David J
AU - Chasman, Daniel I
AU - Chen, Xing
AU - Chen, Xu
AU - Chung, Jonathan
AU - Chutkow, William
AU - Cook, James P
AU - Delgado, Graciela E
AU - Denaxas, Spiros
AU - Doney, Alexander S
AU - Dörr, Marcus
AU - Dudley, Samuel C
AU - Dunn, Michael E
AU - Engström, Gunnar
AU - Esko, Tõnu
AU - Felix, Stephan B
AU - Finan, Chris
AU - Ford, Ian
AU - Ghanbari, Mohsen
AU - Ghasemi, Sahar
AU - Giedraitis, Vilmantas
AU - Giulianini, Franco
AU - Gottdiener, John S
AU - Køber, Lars
AU - Stender, Steen
AU - Torp-Pedersen, Christian
AU - Weeke, Peter E
AU - Regeneron Genetics Center
PY - 2020/1/9
Y1 - 2020/1/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85077697294&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13690-5
DO - 10.1038/s41467-019-13690-5
M3 - Journal article
C2 - 31919418
VL - 11
SP - 163
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 163
ER -