A pediatric perspective on genomics and prevention in the twenty-first century

Abstract

We present evidence from diverse disciplines and populations to identify the current and emerging role of genomics in prevention from both medical and public health perspectives as well as key challenges and potential untoward consequences of increasing the role of genomics in these endeavors. We begin by comparing screening in healthy populations (newborn screening), with testing in symptomatic populations, which may incidentally identify secondary findings and at-risk relatives. Emerging evidence suggests that variants in genes subject to the reporting of secondary findings are more common than expected in patients who otherwise would not meet the criteria for testing and population testing for variants in these genes may more precisely identify discrete populations to target for various prevention strategies starting in childhood. Conversely, despite its theoretical promise, recent studies attempting to demonstrate benefits of next-generation sequencing for newborn screening have instead demonstrated numerous barriers and pitfalls to this approach. We also examine the special cases of pharmacogenomics and polygenic risk scores as examples of ways genomics can contribute to prevention amongst a broader population than that affected by rare Mendelian disease. We conclude with unresolved questions which will benefit from future investigations of the role of genomics in disease prevention.