Polygenic Susceptibility in Peripartum, Alcohol-Induced, and Cancer Therapy–Related Cardiomyopathies

Does a polygenic predisposition to dilated cardiomyopathy (DCM) contribute to peripartum cardiomyopathy (PPCM), alcohol-induced cardiomyopathy (ACM), and cancer therapy–related cardiomyopathy (CCM)?In this cohort study of 1 267 899 individuals, 3414 individuals with PPCM, ACM, and CCM were identified, and a DCM polygenic score was associated with each phenotype. Monogenic DCM variants were enriched but present in few individuals, while a majority had a high polygenic score, conferring an increased risk; most lacked antecedent clinical risk factors.Many patients with PPCM, ACM, and CCM shared a monogenic and polygenic basis with DCM, suggesting that genetic factors may identify populations at risk.

Corresponding Author: Krishna G. Aragam, MD, MS, Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge St, Simches Research Building, 3.128, Boston, MA 02114 (karagam@broadinstitute.org).

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