Genomics-Inspired Biomarkers and Diagnostics—Where Are They?

[摘要] Since the inception of the Human Genome Project in the late 1980s there has been unprecedented growth in the technologies to assay nucleic acids, proteins, and metabolic analytes at scale. One might have expected a concomitant increase in the development and delivery for use in the clinic of genome-inspired biomarkers and diagnostics; but, as this special cardiovascular issue of Clinical Chemistry demonstrates, the field continues to be denominated by old friends such as cardiac troponin I (cTnI),2 B-type natriuretic (BNP), and other single-analyte markers, albeit with greater analytical sensitivity and, as a result, broader potential applicability. It is disappointing not to see more from genomics given that the field of cardiovascular medicine aspires to be more precise in risk assessment, early and accurate diagnosis, and in the treatment and monitoring of disease. Most cardiovascular biomarker and diagnostics have been introduced using disease hypotheses based on known biology. BNP and cTnI are great examples that have revolutionized our ability to distinguish cardiac from pulmonary etiologies of dyspnea, to risk stratify patients with heart failure, and guide therapies in acute coronary syndromes. Unbiased and hypothesis-generating approaches using genomics, transcriptomics, proteomics, and metabolomics have great potential to deliver novel biomarkers and assays for the practice of cardiovascular precision medicine, but have challenges in their path to becoming accepted and useful clinically.Prior to the advent of the first genome-wide association studies (GWAS) in 2005 (1, 2), the literature was littered with association studies using single nucleotide polymorphisms that failed to replicate. The reasons for this were many, including poor study design, insufficient power, the use of “samples of convenience” resulting in confounding by unmeasured variables, and the lack of replication as a requirement for publication. Over the past decade, GWAS have defined the association of genetic variants with a variety of …

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