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BackgroundLeft ventricular maximum wall thickness (LVMWT) is an important biomarker of left ventricular hypertrophy and provides diagnostic and prognostic information in hypertrophic cardiomyopathy (HCM). Limited information is available on the genetic determinants of LVMWT.MethodsWe performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study.ResultsTwenty-one genetic loci were discovered at P<5×10-8. Several novel candidate genes were identified including PROX1, PXN, and PTK2, with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13-1.23]) with pairwise analyses demonstrating a moderate genetic correlation (rg=S0.53) and substantial loci overlap (19/21).ConclusionsOur findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.

Original publication

DOI

10.1161/circgen.122.003716

Type

Journal article

Journal

Circulation. Genomic and precision medicine

Publication Date

01/2023

Addresses

William Harvey Research Institute, Barts and The London School of Medicine and Dentistry (N.A., S.v.D., S.E.P., P.B.M.).