Genetics in Medicine | Commentary
We screen newborns, don’t we?: realizing the promise of public health genomics
- Journal name:
- Genetics in Medicine
- (2013)
- DOI:
- doi:10.1038/gim.2013.11
- Received
- Accepted
- Published online
Genomics and public health have been uneasy bedfellows for some time. Most efforts to improve population health through genomic approaches have focused on the assessment of risks for common diseases, with the aim of tailoring interventions and screening.1 However, the improvement of population health through such an approach has remained elusive.2 Now, rapid progress in affordable, robust DNA sequencing offers a promising opportunity. By expanding the field’s focus from common to rare diseases, it may be possible to realize the promise of public health genomics by identifying those millions of individuals who unknowingly carry mutations that confer a dramatic predisposition to preventable diseases.
In seeking to apply genomic technologies to public health, the traditional focus on common diseases is understandable. After all, even minor progress in risk reduction for diseases that affect millions of people could have a large beneficial impact. In addition, although potential for this approach certainly remains, we have little to show in terms of improved health after more than a decade of such focus. There may be several reasons for a lack of robust progress on this front. First and foremost, genetics constitutes a relatively small etiologic component of common diseases,3 a fact that places an inherent ceiling on the utility of genetic risk assessment. Although the possibility exists that more of the risk for common diseases may be explained by gene–exposure interactions, this hypothesis has yet to be realized. Moreover, common diseases are . . . well, common. Thus, the absolute risk for any individual to develop these diseases will remain substantial regardless of our ability to tweak an individual’s relative risk by genetic analysis. Therefore, the population at large will likely benefit from public health interventions designed to lower that risk, regardless of their precisely quantified relative risk. Further undermining the utility of modestly adjusting one’s risk for common diseases through genomic analysis is the fact that the medical and population prevention tools at our disposal by which to intervene and lower disease risks are blunt, and their use incurs a variety of risks. Experiences with side effects of statins and estrogen replacement therapy for people with modest disease risks show the potential downsides of medical interventions to alter population health risks;4medical interventions are usually most beneficial when identified disease risks and potential benefits are high. Finally, 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.5 Thus far, this notion is largely contradicted by available evidence.5,6 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.7,8
However, recent advances in sequencing technology provide a new opportunity to expand the focus of public health genomics in a way in which its promise can be realized. Millions of people in the United States unknowingly carry (individually rare) mutations that confer dramatic predisposition to preventable diseases. These individuals could readily benefit from existing, validated preventive modalities if knowledge of their underlying genomic risk was available. A case in point is Lynch syndrome. The roughly 0.2% of individuals9 in the US who harbor deleterious mutations in any one of four Lynch-associated genes are at >80% risk for colon cancer.10,11 If their high-risk status is known, validated preventive strategies can dramatically reduce their risk of ever developing cancer.11,12 A number of other genes in the human genome confer very high risk of preventable diseases when mutated, and an aggregate population prevalence of mutations in such genes ranges between 0.5% and 1%. An added benefit of focusing on rare diseases in this manner is that, because of the genetic nature of these disorders, for each at-risk person identified, several other family members are identified who will benefit, thereby amplifying its utility several fold.13 Although the morbidity and mortality that result from carrying such mutations often is preventable, until now the only way of identifying these individuals has been to wait until they or many of their family members develop life-threatening diseases. It is now feasible to consider identifying such individuals through the broad application of rapid and inexpensive sequencing of targeted genes.
In seeking to apply genomic technologies to public health, the traditional focus on common diseases is understandable. After all, even minor progress in risk reduction for diseases that affect millions of people could have a large beneficial impact. In addition, although potential for this approach certainly remains, we have little to show in terms of improved health after more than a decade of such focus. There may be several reasons for a lack of robust progress on this front. First and foremost, genetics constitutes a relatively small etiologic component of common diseases,3 a fact that places an inherent ceiling on the utility of genetic risk assessment. Although the possibility exists that more of the risk for common diseases may be explained by gene–exposure interactions, this hypothesis has yet to be realized. Moreover, common diseases are . . . well, common. Thus, the absolute risk for any individual to develop these diseases will remain substantial regardless of our ability to tweak an individual’s relative risk by genetic analysis. Therefore, the population at large will likely benefit from public health interventions designed to lower that risk, regardless of their precisely quantified relative risk. Further undermining the utility of modestly adjusting one’s risk for common diseases through genomic analysis is the fact that the medical and population prevention tools at our disposal by which to intervene and lower disease risks are blunt, and their use incurs a variety of risks. Experiences with side effects of statins and estrogen replacement therapy for people with modest disease risks show the potential downsides of medical interventions to alter population health risks;4medical interventions are usually most beneficial when identified disease risks and potential benefits are high. Finally, 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.5 Thus far, this notion is largely contradicted by available evidence.5,6 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.7,8
However, recent advances in sequencing technology provide a new opportunity to expand the focus of public health genomics in a way in which its promise can be realized. Millions of people in the United States unknowingly carry (individually rare) mutations that confer dramatic predisposition to preventable diseases. These individuals could readily benefit from existing, validated preventive modalities if knowledge of their underlying genomic risk was available. A case in point is Lynch syndrome. The roughly 0.2% of individuals9 in the US who harbor deleterious mutations in any one of four Lynch-associated genes are at >80% risk for colon cancer.10,11 If their high-risk status is known, validated preventive strategies can dramatically reduce their risk of ever developing cancer.11,12 A number of other genes in the human genome confer very high risk of preventable diseases when mutated, and an aggregate population prevalence of mutations in such genes ranges between 0.5% and 1%. An added benefit of focusing on rare diseases in this manner is that, because of the genetic nature of these disorders, for each at-risk person identified, several other family members are identified who will benefit, thereby amplifying its utility several fold.13 Although the morbidity and mortality that result from carrying such mutations often is preventable, until now the only way of identifying these individuals has been to wait until they or many of their family members develop life-threatening diseases. It is now feasible to consider identifying such individuals through the broad application of rapid and inexpensive sequencing of targeted genes.
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