Rare missense mutations in ACTN2 result in ventricular fibrillation, cardiomyopathy, and sudden death73,74, and a distal variant (rs535411) associated with heart failure in a GWAS75 was in low R2 but high D’ with rs12724121 (D’ = 1; R2 = 0.035, 28.5 kb upstream), suggesting that a potential synthetic association76,77 exists between these two variants. Here, ACTN2 is linked to heart failure.