Imperial College London
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ProfessorSanjayPrasad

Faculty of Medicine, National Heart & Lung Institute

Professor of Cardiomyopathy
 
 
 
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Contact

 

+44 (0)20 7352 8121s.prasad

 
 
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Location

 

CMR UnitRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Harper:2021:10.1038/s41588-020-00764-0,
author = {Harper, AR and Goel, A and Grace, C and Thomson, KL and Petersen, SE and Xu, X and Waring, A and Ormondroyd, E and Kramer, CM and Ho, CY and Neubauer, S and Tadros, R and Ware, JS and Bezzina, CR and Farrall, M and Watkins, H},
doi = {10.1038/s41588-020-00764-0},
journal = {Nature Genetics},
pages = {135--142},
title = {Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity},
url = {http://dx.doi.org/10.1038/s41588-020-00764-0},
volume = {53},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants. We report a genome-wide association study of 2,780 cases and 47,486 controls that identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM (64% of cases; h2g = 0.34 ± 0.02). A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity in sarcomere variant carriers. Mendelian randomization identified diastolic blood pressure (DBP) as a key modifiable risk factor for sarcomere-negative HCM, with a one standard deviation increase in DBP increasing the HCM risk fourfold. Common variants and modifiable risk factors have important roles in HCM that we suggest will be clinically actionable.
AU  - Harper,AR
AU  - Goel,A
AU  - Grace,C
AU  - Thomson,KL
AU  - Petersen,SE
AU  - Xu,X
AU  - Waring,A
AU  - Ormondroyd,E
AU  - Kramer,CM
AU  - Ho,CY
AU  - Neubauer,S
AU  - Tadros,R
AU  - Ware,JS
AU  - Bezzina,CR
AU  - Farrall,M
AU  - Watkins,H
DO  - 10.1038/s41588-020-00764-0
EP  - 142
PY  - 2021///
SN  - 1061-4036
SP  - 135
TI  - Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity
T2  - Nature Genetics
UR  - http://dx.doi.org/10.1038/s41588-020-00764-0
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000611467100003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41588-020-00764-0
UR  - http://hdl.handle.net/10044/1/88293
VL  - 53
ER  -
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