Strauss et al. used MR to examine the associations of the methylene tetrahydrofolate gene and paraoxonase 1 gene variants as a proxy for lifelong exposure to high homocysteine and homocysteine-thiolactone concentrations with the development of heart failure in men aged ≤ 60 years, providing evidence that hyperhomocysteinemia is a causal factor for non-ischemic heart failure in dilated cardiomyopathy (61). This evidence concerns the gene PON1 and heart failure.