Recently, George Church, a prominent genomics researcher and leader of the Personal Genome Project asked why so few people are opting to inspect their genome. The cost and accuracy of genome sequencing have certainly improved dramatically. He clearly sees the health benefits of whole genome sequencing. He states “we should avoid being judgmental of people who practice genomic modesty or who choose not to act on genome information, but we should also ask if we are providing adequate and equal access to education about the benefits and risks of genome information.” Will access and education be sufficient to do the job? Or do we also need additional evidence on the interpretation, utility and value of our genome in health care and disease prevention?
More than a decade after the completion of the human genome project, the genome sequence has reached the clinic. We are now the era of Next Generation Sequencing (NGS) which includes many platforms for sequencing the exome or other large components of the genome, eventually culminating in whole genome sequencing (WGS). These technologies are increasingly utilized to identify genetic causes of rare, mysterious diseases, particularly childhood conditions. In addition, tumor-based genomic screening, family history–directed decision support, and pharmacogenomic applications all show increasing promise in the practice of medicine.
But how about genomic sequencing of healthy individuals? Over the past few years, an increasing number of healthy individuals have had their genomes sequenced, analyzed, and published. The Personal Genome Project has been dedicated to creating public genome, health, and trait data resources and is based on willing participants that agree to publicly share their personal data for improving the health of many. Recently, the Empowered Genome Community initiative was launched to help people who have had their whole genomes sequenced make their genomes more scientifically useful, by exploring and sharing them with each other and with researchers.
But is the routine use of WGS beyond research any different from the use of screening tests in clinical practice? One can argue that WGS is part of the unique characteristics of each person (age, gender, ancestry, ethnicity) and can be used for a variety of purposes other than clinical practice, such as genealogy, recreation, forensics, and health literacy. When it can be measured correctly and the price is right, should it be exempt from evidence-based principles? In fact, many researchers and genomic tests developers are convinced that “consumers want their genomes sequenced, and that they have a right to have them. The only question is the price. When the price comes down far enough, it will just happen. Everyone will get their genomic data and know what to make of it. We will be living in a kind of genomic utopia.”
Nevertheless, if we want to use WGS in the course of regular preventive care and health promotion, research should be conducted to evaluate its benefits, harms and added value to what we are currently doing. The widespread use of cholesterol screening in the population in the prevention of heart disease and prostate specific antigen in screening for prostate cancer are just two examples that have been subjected to years of rigorous studies (the latter is still controversial) and evidence-based guidelines. The idea of screening healthy individuals has been around for more than 100 years and has captured the interest of health-care providers, public health professionals, and the general public. The main purpose of screening is early detection of asymptomatic disease or risk assessment for future disease to improve health outcomes. Today screening is well established in clinical practice and public health and includes many diseases such as cancer, diabetes, heart disease and infectious diseases. Scientific and implementation principles for screening have been discussed by many organizations, most notably the 1968 criteria from the World Health Organization [PDF 7.25 MB], and have evolved over time. These principles ensure that the benefits of screening outweigh potential harms and reach equitably throughout the population. Generally, however, we tend to overestimate the positive health impact of screening and underestimate the potential for harmful effects such as overdiagnosis, inappropriate interventions, and anxiety.
While WGS in healthy individuals has the potential, using genetic risk stratification, for improving health and preventing disease, it can also lead to potential medical and psychological harms, cascading or inappropriate healthcare interventions and increasing costs. Given the myriad of weak associations between genetic variants and many diseases, it is not currently clear what the added value of genomic information is in screening and disease prevention [PDF 641.24 KB]. As stated by Evans and colleagues in a recent commentary: “Efforts that aim for genomic risk stratification often are justified by the hope that simply informing individuals of their genetic risks for disease will induce beneficial behavioral changes. Thus far, this notion is largely contradicted by available evidence. Although we already know how to lower risks for most common diseases, getting populations to eat properly, exercise, and give up unhealthy behaviors, especially without major policy changes, is challenging, and there is little evidence to suggest that genetic tweaking of risk will meaningfully augment these efforts.” The bottom line is that we still do not understand the balance of benefits and harms of WGS and how to ensure that benefits can be distributed equitably across the population. The importance of conducting research on WGS before widespread use in practice cannot be over emphasized.
It is important to remember that WGS is not one test. It is a conglomerate of numerous tests, millions of genetic variants, a few of them have been validated for use in specific practice scenarios (such as Lynch Syndrome and Hereditary Breast and Ovarian Cancer, but the vast majority of genomic variants are of unknown health or medical significance. Therefore, as part of “rolling out” the WGS in practice, it is crucial to put its various components into “bins” of increasing levels of evidence on validity and utility to ensure reaping the full benefits of this far reaching technology in improving population health.
We hope that current National Human Genome Research Institute genomic medicine implementation activities will assess whether and how to implement next generation sequencing (NGS) into clinical practice both in sick people as well as healthy populations. Currently, a number of academic centers are studying implementation of genomic medicine in various research projects. In addition, the National Cancer Institute funded several comparative effectiveness research projects in cancer genomics to evaluate the added-value of genomic tests and applications along the cancer care continuum.
Finally, it is worth noting that the NIH recently awarded grants totaling more than $25 million over four years to help three research groups to develop authoritative information on the millions of genomic variants relevant to human disease and the hundreds that are expected to be useful for clinical practice. This effort will lead the way towards an evidence-based integration of the WGS into medicine and public health.