Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience

Journal article

S. Jurgens, Joel T. Rämö, D. Kramarenko, L. Wijdeveld, J. Haas, M. Chaffin, S. Garnier, L. Gaziano, L. Weng, Alex Lipov, Sean L. Zheng, Albert Henry, J. Huffman, Saketh Challa, Frank Rühle, Carmen Diaz Verdugo, C. Krijger Juárez, S. Kany, C. A. van Orsouw, K. Biddinger, E. Poel, Amanda L. Elliott, Xin Wang, C. Francis, Richard Ruan, S. Koyama, L. Beekman, Dominic S Zimmerman, J. Deleuze, E. Villard, D. Trégouët, R. Isnard, Joel T. Amanda L. Juha Teemu Jari Aarno Mark Rämö Elliott Sinisalo Niiranen Laukkanen Palotie D, J. Sinisalo, T. Niiranen, J. Laukkanen, A. Palotie, Mark Daly, Jennifer E. Kyong-Mi Philip S. Krishna G. Huffman Chang Tsao Aragam, Kyong-Mi Chang, Phil Tsao, Krishna G. Aragam, Sean L. Albert Kiran James S. R. Thomas Patrick T. Kris Zheng Henry Biddinger Ware Lumbers Ellinor Aragam, James S. Ware, R. Lumbers, P. Ellinor, D. Boomsma, E. D. de Geus, R. Tadros, Y. Pinto, A. Wilde, J. Hottenga, Roddy Walsh, A. F. Schmidt, Seung Hoan Choi, P. Matthews, S. N. van der Crabben, A. Amin, P. Charron, B. Meder, C. Bezzina
Nature Genetics, 2024

Semantic Scholar DOI PubMedCentral PubMed

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APA Click to copy
Jurgens, S., Rämö, J. T., Kramarenko, D., Wijdeveld, L., Haas, J., Chaffin, M., … Bezzina, C. (2024). Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience. Nature Genetics.

Chicago/Turabian Click to copy
Jurgens, S., Joel T. Rämö, D. Kramarenko, L. Wijdeveld, J. Haas, M. Chaffin, S. Garnier, et al. “Genome-Wide Association Study Reveals Mechanisms Underlying Dilated Cardiomyopathy and Myocardial Resilience.” Nature Genetics (2024).

MLA Click to copy
Jurgens, S., et al. “Genome-Wide Association Study Reveals Mechanisms Underlying Dilated Cardiomyopathy and Myocardial Resilience.” Nature Genetics, 2024.

BibTeX Click to copy

@article{s2024a,
  title = {Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience},
  year = {2024},
  journal = {Nature Genetics},
  author = {Jurgens, S. and Rämö, Joel T. and Kramarenko, D. and Wijdeveld, L. and Haas, J. and Chaffin, M. and Garnier, S. and Gaziano, L. and Weng, L. and Lipov, Alex and Zheng, Sean L. and Henry, Albert and Huffman, J. and Challa, Saketh and Rühle, Frank and Verdugo, Carmen Diaz and Juárez, C. Krijger and Kany, S. and van Orsouw, C. A. and Biddinger, K. and Poel, E. and Elliott, Amanda L. and Wang, Xin and Francis, C. and Ruan, Richard and Koyama, S. and Beekman, L. and Zimmerman, Dominic S and Deleuze, J. and Villard, E. and Trégouët, D. and Isnard, R. and D, Joel T. Amanda L. Juha Teemu Jari Aarno Mark Rämö Elliott Sinisalo Niiranen Laukkanen Palotie and Sinisalo, J. and Niiranen, T. and Laukkanen, J. and Palotie, A. and Daly, Mark and Aragam, Jennifer E. Kyong-Mi Philip S. Krishna G. Huffman Chang Tsao and Chang, Kyong-Mi and Tsao, Phil and Aragam, Krishna G. and Aragam, Sean L. Albert Kiran James S. R. Thomas Patrick T. Kris Zheng Henry Biddinger Ware Lumbers Ellinor and Ware, James S. and Lumbers, R. and Ellinor, P. and Boomsma, D. and de Geus, E. D. and Tadros, R. and Pinto, Y. and Wilde, A. and Hottenga, J. and Walsh, Roddy and Schmidt, A. F. and Choi, Seung Hoan and Matthews, P. and van der Crabben, S. N. and Amin, A. and Charron, P. and Meder, B. and Bezzina, C.}
}

Abstract

Dilated cardiomyopathy (DCM) is a heart muscle disease that represents an important cause of morbidity and mortality, yet causal mechanisms remain largely elusive. Here, we perform a large-scale genome-wide association study and multitrait analysis for DCM using 9,365 cases and 946,368 controls. We identify 70 genome-wide significant loci, which show broad replication in independent samples and map to 63 prioritized genes. Tissue, cell type and pathway enrichment analyses highlight the central role of the cardiomyocyte and contractile apparatus in DCM pathogenesis. Polygenic risk scores constructed from our genome-wide association study predict DCM across different ancestry groups, show differing contributions to DCM depending on rare pathogenic variant status and associate with systolic heart failure across various clinical settings. Mendelian randomization analyses reveal actionable potential causes of DCM, including higher bodyweight and higher systolic blood pressure. Our findings provide insights into the genetic architecture and mechanisms underlying DCM and myocardial function more broadly. Genome-wide association and multitrait analyses for dilated cardiomyopathy (DCM) using 9,365 cases and 946,368 controls provide insights into the mechanisms underlying DCM and myocardial resilience