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@article{Tadros:2023:10.1101/2023.01.28.23285147,
author = {Tadros, R and Zheng, SL and Grace, C and Jordà, P and Francis, C and Jurgens, SJ and Thomson, KL and Harper, AR and Ormondroyd, E and West, DM and Xu, X and Theotokis, PI and Buchan, RJ and McGurk, KA and Mazzarotto, F and Boschi, B and Pelo, E and Lee, M and Noseda, M and Varnava, A and Vermeer, AM and Walsh, R and Amin, AS and van, Slegtenhorst MA and Roslin, N and Strug, LJ and Salvi, E and Lanzani, C and de, Marvao A and Hypergenes, InterOmics Collaborators and Roberts, JD and Tremblay-Gravel, M and Giraldeau, G and Cadrin-Tourigny, J and L'Allier, PL and Garceau, P and Talajic, M and Pinto, YM and Rakowski, H and Pantazis, A and Baksi, J and Halliday, BP and Prasad, SK and Barton, PJ and O'Regan, DP and Cook, SA and de, Boer RA and Christiaans, I and Michels, M and Kramer, CM and Ho, CY and Neubauer, S and HCMR, Investigators and Matthews, PM and Wilde, AA and Tardif, J-C and Olivotto, I and Adler, A and Goel, A and Ware, JS and Bezzina, CR and Watkins, H},
doi = {10.1101/2023.01.28.23285147},
journal = {medRxiv},
title = {Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.},
url = {http://dx.doi.org/10.1101/2023.01.28.23285147},
year = {2023}
}

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TY  - JOUR
AB  - Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality with both monogenic and polygenic components. We here report results from the largest HCM genome-wide association study (GWAS) and multi-trait analysis (MTAG) including 5,900 HCM cases, 68,359 controls, and 36,083 UK Biobank (UKB) participants with cardiac magnetic resonance (CMR) imaging. We identified a total of 70 loci (50 novel) associated with HCM, and 62 loci (32 novel) associated with relevant left ventricular (LV) structural or functional traits. Amongst the common variant HCM loci, we identify a novel HCM disease gene, SVIL, which encodes the actin-binding protein supervillin, showing that rare truncating SVIL variants cause HCM. Mendelian randomization analyses support a causal role of increased LV contractility in both obstructive and non-obstructive forms of HCM, suggesting common disease mechanisms and anticipating shared response to therapy. Taken together, the findings significantly increase our understanding of the genetic basis and molecular mechanisms of HCM, with potential implications for disease management.
AU  - Tadros,R
AU  - Zheng,SL
AU  - Grace,C
AU  - Jordà,P
AU  - Francis,C
AU  - Jurgens,SJ
AU  - Thomson,KL
AU  - Harper,AR
AU  - Ormondroyd,E
AU  - West,DM
AU  - Xu,X
AU  - Theotokis,PI
AU  - Buchan,RJ
AU  - McGurk,KA
AU  - Mazzarotto,F
AU  - Boschi,B
AU  - Pelo,E
AU  - Lee,M
AU  - Noseda,M
AU  - Varnava,A
AU  - Vermeer,AM
AU  - Walsh,R
AU  - Amin,AS
AU  - van,Slegtenhorst MA
AU  - Roslin,N
AU  - Strug,LJ
AU  - Salvi,E
AU  - Lanzani,C
AU  - de,Marvao A
AU  - Hypergenes,InterOmics Collaborators
AU  - Roberts,JD
AU  - Tremblay-Gravel,M
AU  - Giraldeau,G
AU  - Cadrin-Tourigny,J
AU  - L'Allier,PL
AU  - Garceau,P
AU  - Talajic,M
AU  - Pinto,YM
AU  - Rakowski,H
AU  - Pantazis,A
AU  - Baksi,J
AU  - Halliday,BP
AU  - Prasad,SK
AU  - Barton,PJ
AU  - O'Regan,DP
AU  - Cook,SA
AU  - de,Boer RA
AU  - Christiaans,I
AU  - Michels,M
AU  - Kramer,CM
AU  - Ho,CY
AU  - Neubauer,S
AU  - HCMR,Investigators
AU  - Matthews,PM
AU  - Wilde,AA
AU  - Tardif,J-C
AU  - Olivotto,I
AU  - Adler,A
AU  - Goel,A
AU  - Ware,JS
AU  - Bezzina,CR
AU  - Watkins,H
DO  - 10.1101/2023.01.28.23285147
PY  - 2023///
TI  - Large scale genome-wide association analyses identify novel genetic loci and mechanisms in hypertrophic cardiomyopathy.
T2  - medRxiv
UR  - http://dx.doi.org/10.1101/2023.01.28.23285147
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36778260
ER  -

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