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@inproceedings{De:2021:eurheartj/ehab724.1731,
author = {De, Marvao A and McGurk, K and Zheng, S and Thanaj, M and Bai, W and Duan, J and Halliday, B and Pantazis, A and Prasad, S and Rueckert, D and Walsh, R and Ho, C and Cook, S and Ware, J and O'Regan, D},
doi = {eurheartj/ehab724.1731},
pages = {1731--1731},
publisher = {European Society of Cardiology},
title = {Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes in over 200,000 adults},
url = {http://dx.doi.org/10.1093/eurheartj/ehab724.1731},
year = {2021}
}

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TY  - CPAPER
AB  - BackgroundHypertrophic 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.PurposeTo determine the population prevalence of HCM-associated sarcomeric variants, characterise their phenotypic manifestations, estimate penetrance, and identify associations between sarcomeric variants and clinical outcomes, we performed an observational study of 218,813 adults in the UK Biobank (UKBB), of whom 200,584 have whole exome sequencing (WES).MethodsWe carried out an integrated analysis of WES and cardiac magnetic resonance (CMR) imaging in UK Biobank participants stratified by sarcomere-encoding variant status. Computer vision techniques were used to automatically segment the four chambers of the heart (Figure 1). Cardiac motion analysis was used to derive strain and strain rates. Regional analysis of left ventricular wall thickness was performed using three-dimensional modelling of these segmentations.ResultsMedian age at recruitment was 58 (IQR 50–63 years), and participants were followed up for a median of 10.8 years (IQR 9.9–11.6 years) with a total of 19,507 primary clinical events reported.The prevalence of rare variants (allele frequency <0.ehab724.17314) in HCM-associated sarcomere-encoding genes in 200,584 participants was 2.9% (n=5,727; 1 in 35), and the prevalence of pathogenic or likely pathogenic variants (SARC-P/LP) was 0.24% (n=474, 1 in 423).SARC-P/LP variants were associated with increased risk of death or major adverse cardiac events (MACE) compared to controls (HR 1.68, 95% CI 1.37–2.06, p<0.001), mainly due to heart failure endpoints (Figure 2: cumulative hazard curves with zoomed plots for lifetime risk of A) death and MACE or B) heart failure, stratified by genotype; genotype negative (SARC-NEG), carriers of indeterminate sarcomeric variants (SARC-IND) or SARC-P/LP; C) Forest plot of comparative lifetime risk of c
AU  - De,Marvao A
AU  - McGurk,K
AU  - Zheng,S
AU  - Thanaj,M
AU  - Bai,W
AU  - Duan,J
AU  - Halliday,B
AU  - Pantazis,A
AU  - Prasad,S
AU  - Rueckert,D
AU  - Walsh,R
AU  - Ho,C
AU  - Cook,S
AU  - Ware,J
AU  - O'Regan,D
DO  - eurheartj/ehab724.1731
EP  - 1731
PB  - European Society of Cardiology
PY  - 2021///
SN  - 0195-668X
SP  - 1731
TI  - Outcomes and phenotypic expression of rare variants in hypertrophic cardiomyopathy genes in over 200,000 adults
UR  - http://dx.doi.org/10.1093/eurheartj/ehab724.1731
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000720456901832&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://academic.oup.com/eurheartj/article/42/Supplement_1/ehab724.1731/6394929
UR  - http://hdl.handle.net/10044/1/94009
ER  -

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