Imperial College London
Alternate

Dr John Baksi

Faculty of Medicine, National Heart & Lung Institute

Honorary Clinical Senior Lecturer
 
 
 
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j.baksi

 
 
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Location

 

Cardiovascular MR UnitRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{de:2021:10.1101/2021.01.21.21249470,
author = {de, Marvao A and McGurk, KA and Zheng, SL and Thanaj, M and Bai, W and Duan, J and Biffi, C and Mazzarotto, F and Statton, B and Dawes, TJW and Savioli, N and Halliday, BP and Xu, X and Buchan, RJ and Baksi, AJ and Quinlan, M and Tokarczuk, P and Tayal, U and Francis, C and Whiffin, N and Theotokis, PI and Zhang, X and Jang, M and Berry, A and Pantazis, A and Barton, PJR and Rueckert, D and Prasad, SK and Walsh, R and Ho, CY and Cook, SA and Ware, JS and ORegan, DP},
doi = {10.1101/2021.01.21.21249470},
title = {Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes amongst UK Biobank participants},
url = {http://dx.doi.org/10.1101/2021.01.21.21249470},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Hypertrophic cardiomyopathy (HCM) is caused by rare variants in sarcomere-encoding genes, but little is known about the clinical significance of these variants in the general population.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We compared outcomes and cardiovascular phenotypes in UK Biobank participants with whole exome sequencing stratified by sarcomere-encoding variant status.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The prevalence of rare variants (allele frequency <0.00004) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), of which 0.24% (n=474, 1 in 423) were pathogenic or likely pathogenic variants (SARC-P/LP). SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events compared to controls (HR 1.68, 95% CI 1.37-2.06, p<0.001), mainly due to heart failure (HR 4.40, 95% CI 3.22-6.02, p<0.001) and arrhythmia (HR 1.55, 95% CI 1.18-2.03, p=0.002). In 21,322 participants with cardiac magnetic resonance imaging, SARC-P/LP were associated with increased left ventricular maximum wall thickness (10.9±2.7 vs 9.4±1.6 mm, p<0.001) and concentric remodelling (mass/volume ratio: 0.63±0.12 vs 0.58±0.09 g/mL, p<0.001), but hypertrophy (≥13mm) was only present in 16% (n=7/43, 95% CI 7-31%). Other rare sarcomere-encoding variants had a weak effect on wall thickness (9.5±1.7 vs 9.4±1.6 mm, p=0.002) with no combined excess cardiovascular risk (HR 1.00 95% CI 0.92-1.08, p=0.9).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>In the general population, SARC-P/LP variants have low aggregate penetrance for overt HCM bu
AU  - de,Marvao A
AU  - McGurk,KA
AU  - Zheng,SL
AU  - Thanaj,M
AU  - Bai,W
AU  - Duan,J
AU  - Biffi,C
AU  - Mazzarotto,F
AU  - Statton,B
AU  - Dawes,TJW
AU  - Savioli,N
AU  - Halliday,BP
AU  - Xu,X
AU  - Buchan,RJ
AU  - Baksi,AJ
AU  - Quinlan,M
AU  - Tokarczuk,P
AU  - Tayal,U
AU  - Francis,C
AU  - Whiffin,N
AU  - Theotokis,PI
AU  - Zhang,X
AU  - Jang,M
AU  - Berry,A
AU  - Pantazis,A
AU  - Barton,PJR
AU  - Rueckert,D
AU  - Prasad,SK
AU  - Walsh,R
AU  - Ho,CY
AU  - Cook,SA
AU  - Ware,JS
AU  - ORegan,DP
DO  - 10.1101/2021.01.21.21249470
PY  - 2021///
TI  - Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes amongst UK Biobank participants
UR  - http://dx.doi.org/10.1101/2021.01.21.21249470
ER  -
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