Key result
An LVESV polygenic score is linked to ~54% greater incident DCM risk per SD.
Why the study?
Dilated cardiomyopathy is an important cause of heart failure, but while many rare variants are known, common variant studies have yielded few associated loci.
Does a polygenic score for left ventricular end systolic volume predict incident dilated cardiomyopathy in previously disease-free individuals?
Observational (n=29,041)
Does a polygenic score for left ventricular end systolic volume predict incident dilated cardiomyopathy in previously disease-free individuals?
Effect estimate: HR 1.54 per 1 SD increase
p-value: p=2.1x10^-16
Common genetic polymorphisms and a polygenic score for left ventricular end systolic volume are significantly associated with cardiac structure, function, and the risk of incident dilated cardiomyopathy.
May refine DCM risk stratification; extends polygenic insights but leaves clinical adoption unproven pending validation.
Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we conducted a genome-wide association study (GWAS) of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 29,041 UK Biobank participants. 26 novel loci were associated with cardiac structure and function. These loci were found near 17 genes previously shown to cause Mendelian cardiomyopathies. A polygenic score of left ventricular end systolic volume was associated with incident DCM in previously disease-free individuals (hazard ratio = 1.54 per one standard deviation increase in the polygenic score, P = 2.1×10 −16 ). Even among carriers of truncating mutations in TTN , the polygenic score influenced the size and function of the heart. These results further implicate common genetic polymorphisms in DCM pathogenesis.
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Pirruccello et al. (2020) conducted an observational in Dilated cardiomyopathy (n=29,041). Polygenic score of left ventricular end systolic volume was evaluated on Incident dilated cardiomyopathy in previously disease-free individuals (HR 1.54 per 1 SD increase, p=2.1x10^-16). A polygenic score of left ventricular end systolic volume was associated with incident dilated cardiomyopathy in previously disease-free individuals (HR 1.54 per 1 SD increase, P=2.1x10^-16).
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