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Managing Health in the Genomic Era
The clinical importance of family health history has long been known and is a proven approach for assessing a patient’s future disease risk. When we conducted a program in primary care practices to increase the awareness and use of family health history for assessing cancer risk years ago, we found that about one-fourth of the patients who volunteered for our pilot study reported a family history of cancer that indicated the need for further evaluation and evidence-based intervention. On the other hand, a retrospective analysis revealed that less than 5% of patient records contained enough family health information to do a meaningful risk assessment. We also learned that physicians are confused about what family information is important to gather. Some also noted that they did not truly understand the role of genetic counselors in the process and were uncertain about the value and limitations of genetic testing for a patient and other family members. The growth of direct to consumer testing results further confounded the issue for both patient and provider. Because there’s uncertainty about how to use it, family health history is underutilized and sometimes misinterpreted when managing a healthy patient.
By no measure does this book, Managing Health in the Genomic Era, comprehensively address the genetic principles involved when a patient with a family history for a chronic condition or disease enters the clinic, but there are some features of our individual gene collections known as the genome, that underlie our family health history. Each of us carries two copies of each of our 22,000 genes – we inherited one from each parent. When we look more closely, we find that many of the gene copies we inherited include DNA sequence variants. Each gene performs specific functions in cells, and each one of us carries 4-5 million variants from the human ‘reference genome’ that are scattered among our chromosomes. Each of us adds several dozen new variants to the collection we inherited which in turn, we might pass along to our own descendants.
Where do our variants come from and what is their importance? Several million variants have been passed along in the human population for thousands of years from distant ancestral founders. These variants have reached so many descendants in present-day populations that they are detected in population screens and entered in to the Human Genome Database. Most of them have no medical consequence that we know, but a few are important. For example, a handful of variants in a gene that normally regulates the repair of (unavoidable) DNA damage in our cells, BRCA1, has been traced back thousands of years in the Ashkenazi Jewish population. Today’s carriers of these variants are at a heightened risk for developing breast/ovarian cancer. All of us also carry thousands of lineage specific variants shared only by present-day descendants of an ancestral founder (that is, the person in whom the variant arose) in the last few centuries. Owing to the explosion of the human population that has occurred in that time, there has also been an explosion of such ‘rare’ genetic variants. We often lack enough clinical information about ‘rare’ variants to draw a conclusion about their impact on disease risk. Even for well-known cancer genes, such as BRCA1, the impact of ‘rare’ variants on cancer risk in this gene is uncertain without testing other carriers and obtaining their personal health history.
Disease risk assessment based on family health history will certainly remain an essential clinical activity as long as diagnostic tests yield negative results or reveal novel genetic variants. Further, we know little about what 80 percent of human genes do at the molecular level nor how a variant of those genes would alter the risk for a chronic disease. As illustrated in the book, finding a pattern of disease among family members occasionally reveals an inherent risk, even if it is impractical to pinpoint a specific genetic variant.
Genetic variants are often described as causal for disease. Indeed, variants sometimes disrupt cellular function enough to cause disease, but usually the effect is subtle and increases the later risk for chronic disease onset, that is, the variant is predisposing. By corollary, health status depends on the interaction of specific genes with the environment. Those carrying certain genetic variants may be vulnerable, but the environment pulls the trigger for health status changes. Who are most likely to share disease predisposing genetic variants? Other family members. A recent report of family members suffering a severe response to Covid-19 infection and carrying ‘rare’ variants of genes involved in immune response is a dramatic illustration of a familial vulnerability revealed by the presence of the virus1.
Despite the rapid progress the Human Genome Project has brought to our knowledge about chronic disease, understanding the specific mechanisms involving the genome remains a work in progress with a long timeline. Alas, we are a long way from practicing personalized molecular medicine on a broad scale. At this moment, therefore, family health history provides us with the quickest, cheapest, and easiest way to obtain information about a patient’s disease risk. Familial clinical information can also serve as a driver for greater personalization simply because genetically similar subjects share inherent tendencies.
The book also notes several of the emerging trends associated with the expansion of family health history in clinical care, including the use of electronic health records for compiling, updating, and analyzing family information, the development of updated clinical flow models2 [Figure Reference], approaches for gathering expanded family pedigrees, an overview of recent research exploring epigenetic mechanisms, and the ascendant role of genetic counseling as an essential component of modern medical practice.
The book’s overall goal became apparent in our prior efforts to expand the use of family health history in our practices and projects. The family unit offers a way to track and treat inherent and chronic disease risks before the occurrence of a disabling health event. By employing family information providers can offer better health management and clinical researchers can devise novel strategies to reduce the incidence and severity of life-threatening and life-limiting conditions.
About the book
- Presents a practical, accessible resource for primary care providers, allied health professionals, pharmacologists, public health professionals, students and clinical researchers
- Addresses genetic and genomic approaches in managing patient health, conducting and analyzing family health histories, and assessing adult disease risk
- Features an expert author team with direct experience integrating genetics and genomics in primary care and family medicine settings
- Examines the attributes and limitations of family health history, genetic testing, and genomic testing in clinical practice
- Includes detailed explanations following practice-based examples
- van der Made CI, Simons A, Schuurs-Hoeijmakers J, et al. Presence of Genetic Variants Among Young Men With Severe COVID-19 [published online ahead of print, 2020 Jul 24]. JAMA. 2020;e2013719. doi:10.1001/jama.2020.13719
- Henrich. VC, Orlando, LA, and Shirts, BH (2020) Managing Health in the Genomic Era.
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