DNA Methylation and Human Heart Failure
Mechanisms or Prognostics
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Article, see p 1528
Heart failure is a growing public health concern, affecting 20% of individuals at some point in their lifetime and contributing to 11% of deaths, with an incidence that is expected to rise by 25% over the next 15 years.1 As a condition that can develop asymptomatically for years, after which the efficacies of most interventions are modest and palliative, heart failure is a prime target for the development of novel biomarkers that could be used in a clinical setting for stratification or as prognostic markers detectable before clinical presentation (the ultimate prize).
Are the tools of high-throughput biology, so-called ’omics investigations, up to the task? Discovery technologies and their analytic platforms, especially for genomics, epigenomics, and transcriptomics, are comprehensive and, if not fully mature, rapidly approaching that point, whereas other ’omics techniques such as proteomics, metabolomics, and lipidomics are increasingly quantitative, reproducible, and amenable to application outside specialized laboratories. These approaches have been widely applied to lower organisms and, at an increasing rate, in the clinical setting. Get on with it then, one might argue, and use these methods to improve human cardiovascular health on a population scale.
If only it were so easy. Genetic variability is a massive confounder in the study of common disease in large human populations. Many of the most successful and largest cohort studies are characterized by modest ethnic and genetic diversity. Syndromes such as heart failure are polygenic, and genome-wide association studies have identified only a few causal variants, each of which explains only a small fraction of the genetic basis of the syndrome. Add to this the contribution of environmental factors, and it is easy to see why current …