The “omics” revolution represents truly personalized, precision medicine. The term “omics” has penetrated virtually every field of the biological sciences and medicine. Practitioners can be sure that wherever a gene encodes for a protein, there is, or soon will be, an “omics” specialty. In this article, we will provide an overview of how genomics is being used in clinical practice today.
Genes provide the underlying mechanisms for all processes involved in human disease or human health. Variations in genes can lead to altered function of the proteins they produce. Interactions with environmental variables can further exacerbate the impact of these genes, leading to a higher risk for cellular, biochemical, and metabolic dysregulation.
Results from the Human Genome Project and the 1,000 Genomes Project Consortium have provided the springboard to new scientific disciplines, such as functional genomics and personalized genomics. These disciplines, in turn, promote the development of improved diagnostic testing, prognosis, and therapeutics concomitant with DNA-directed prevention and treatment strategies. Some refer to this endeavor as the Precision Medicine Initiative, although in the broader context it can be thought of as all under the umbrella of genomics. Regardless of what you call it, genomics has and will continue to transform medicine one patient at a time.
The integration of genomics with clinical medicine is probably best illustrated today in the area of pharmacogenomics; it allows a clinician to “unzip” a patient’s DNA, identifying gene variants associated with a response to OTC and prescribed medications. Adverse medication reactions are becoming an increasingly prevalent problem, estimated to cost more than $3 billion annually. With more than 50 percent of American adults using at least one pharmaceutical intervention on a regular basis and 15 percent using five or more medications, pharmacogenomics can provide an effective solution to improve patient outcomes and decrease costs.
Adverse reactions can be caused by gene-medication interactions as well as drug-drug interactions. Efficacy of medications is also impacted by a person’s genotype. For example, many common opioids are actually prodrugs, and must be converted into active form. An individual with a slow metabolizer genotype for CYP2D6 will have inefficient conversion of codeine to morphine, resulting in inadequate pain relief. A fast metabolizer, on the other hand, has an increased risk of morphine toxicity due to more rapid conversion of codeine.
Pharmacogenomic testing can be even more effective as a preventative tool. Based on known population frequencies of the 12 genes most commonly tested in pharmacogenomics, 99 percent of the population is likely to carry at least one of these variants. A recent study by the Mayo Clinic confirmed this. In the research, 99 percent of study subjects contained at least one of the five tested pharmacogenomic gene variants. They also found that 89 percent had two or more, which supports proactively testing a patient’s genotype involved in drug metabolism and response before prescribing a medication.
Oncogenomics involves examining the DNA of a cancerous tumor to personalize a drug treatment. This approach can lead to increased efficacy of cancer therapy and can identify treatment modalities to reduce the probability of the tumor developing resistance to a long-term cancer medication. When used in combination with pharmacogenomics, oncogenomics can also help to minimize drug side-effects for the patient.
Currently, oncogenomics is primarily being used in specialty cancer centers, where oncologists are looking for better answers for patients who have not responded well to standard therapy, have had recurrence of particularly aggressive cancers, or have tumors that are known to respond differentially to treatments based on established genomic subtypes. HER2 breast cancer and EGFR lung cancer are two examples where oncogenomics is being used clinically with improved outcomes. While not a panacea for all cancers, oncogenomics has helped researchers discover that cancer genes have plasticity–they can change in response to their environment. This unexpected challenge is providing more clues about cellular biology, and hopefully more efficient ways to develop effective treatments for patients who are refractory to current treatment protocols.
But you don’t have to have a cancer diagnosis to benefit from the genomic revolution. Genomics, genomic testing, and the interpretation of those results are transforming the practice of medicine in other areas, including nutrition and behavioral sciences.
Personalized genomics compares the genotype of an individual using either single nucleotide polymorphisms (SNPs), partial, or full genome sequencing to published research to determine a person’s predisposition to a disease such as diabetes, obesity, or osteoporosis, to name a few. Improving the health and well-being of an individual, mitigating the effects of gene SNPs on cellular biology, biochemical, and metabolic pathways by personalizing lifestyle, nutritional, and dietary recommendations are but a few ways genomics has revolutionized preventive medicine.
Nutrition scientists are using a subcategory of genomics called nutritional genomics to better understand why people respond differently to the foods they eat. Nutritional genomics is the study of how our genes and food interact, and it is helping explain why a one-size-fit-all approach to diet has been ineffective in stemming the tide of diet and lifestyle-related chronic disease. Furthermore, nutritional genomics can explain why some people are more susceptible to diabetes or obesity when on a high carbohydrate diet; why certain foods are more helpful for addressing health issues in some people but not others; and why nutritional requirements can vary from person to person. By understanding a person’s genotype, clinicians can tailor dietary interventions to each individual.
The field of nutritional genomics is subdivided into two areas: nutrigenetics and nutrigenomics. Nutrigenetics is defined as the influence of genes on nutrient utilization, or how our genes can alter how we absorb, digest, assimilate and utilize nutrients in our foods. Nutrigenomics is defined as the influence of food or food constituents on gene function and health.
An example of nutrigenetics is omega fatty acid metabolism. The enzyme involved in the rate-limiting step in conversion from omega-3 fatty acid precursors to eicosopentanoic acid (EPA) is delta-5 desaturase. This enzyme is also involved in the parallel pathway of omega-6 fatty acid precursor conversion to arachidonic acid, but for the purposes of this article we will focus on the omega-3 pathway.
Delta-5 desaturase enzyme is encoded by the FADS1 gene. A SNP on the FADS1 gene impairs activity of the enzyme, resulting in reduced production of EPA. For the person that relies solely on plant based omega-3 sources, there is a risk of an EPA deficiency. Recent studies have shown that the frequency of this SNP in humans has changed over time, with a lower penetration in agrarian societies that relied primarily on plants for food, and a higher penetration in societies where diets were rich in animal proteins that directly supplied EPA.
An example of nutrigenomics is the antioxidant cascade. Nutrient cofactors are needed for many enzymatic reactions, and these are supplied through our diet in the form of vitamins and minerals. There are non-nutrient components of foods that also affect enzyme activity through regulation of the genes that encode them. These are called bioactives. Some of the most commonly known bioactives are flavones, including resveratrol, which upregulates Nrf2 activity to provide a greater endogenous antioxidant response. Nutrigenomics can be used in a generalized way to boost the overall health of a population. It is even more effective when used as part of a comprehensive nutritional genomic strategy directed by an individual’s unique genotype.
Culinary genomics is a pioneering approach to food as medicine that was developed by our colleague, Amanda Archibald, RD, and introduced to clinicians in the U.S. in 2015. Culinary Genomics blends the sciences of nutrition and genomics with the culinary arts to boost dietary bioactives with known nutrigenomic activity on a whole food, nutrient-dense canvas. Amanda recognized that translating nutrigenomic and nutrigenetic recommendations onto a person’s plate requires knowledge of not only the principles of genomics but also the culinary arts.
The principles of culinary genomics teach people how to use whole foods rich in bioactives, nutrients, and co-factors as part of a well-thought-out nutritional genomic strategy based on the individual’s own DNA blueprint. With this approach, food is at the center of the intervention, and nutritional supplements are then used to address specific gaps and needs. Culinary genomics can easily be used by health and nutritional professionals using diet and lifestyle strategies for patients, and by forward-thinking chefs eager to use this new approach to differentiate their menus. It is also at the forefront of changing the food-gene conversation at a public health level.
The study of genomes of the aerobic and anaerobic microorganisms that live in the digestive tract of humans is called microbiomics. Once considered an afterthought in a traditional medical practice, the microbiome is now front and center in the quest to better understand chronic illnesses that impact nearly all of the world’s populations.
Advances in omics-technology are providing a better picture of the quantitative and qualitative aspects of microorganisms in the gastrointestinal (GI) tract. Research shows how macro and micronutrients and bioactives found in food play a role in supporting a healthy microbiome, and how imbalances between and among the microflora can precipitate pro-inflammatory reactions, leading to local and systemic disease-inducing conditions. Microbial imbalances can lead to deficiencies in micronutrient absorption and utilization. Testing to identify these imbalances can lead to a better understanding of the many unanswered questions as to the function of each bacterial subtype, how variations can impact health, how colonies of different bacteria work together (or not) and how direct interventions can lead to specific changes in the microbiome itself.
All oral medications pass through the GI tract, and it did not take long for scientists to realize that variations within the human microbiome can alter drug absorption, metabolism, and detoxification. While a relatively new area to the “omics” family, pharmacomicrobiomics, will be no doubt contribute immensely to a better understanding of pharmacokinetics, drug efficacy, and improved drug delivery.
Another member of the “omics” revolution is epigenomics, which literally translated means “above the genome”. Epigenomics, frequently used interchangeably with the term epigenetics, is the study of the locations and functions of chemical tags on the DNA of human genome that do not alter the DNA itself, but can alter gene expression and chronic disease risk in current and subsequent generations of individuals.
While many equate the nutritional genomics involved in the transmethylation and transsulfuration cycles as equivalent to epigenetics, this is only part of the equation. The process of epigenomics is complex, and these chemical tags involve many different processes, including DNA methylation; histone modification (acetylation, methylation, ubiquitinylation, and phosphorylation); and non-coding microRNA. These processes rely on genes involved in cell signaling and various transfer enzymes encoded by a wide array of genes.
While we have gained much knowledge in how epigenetic changes alter gene expression and health, and how our diet and lifestyle can influence these changes, we do not yet have robust data to direct interventions specifically. The availability of accurate testing of the epigenome is still out of reach for clinicians and patients, existing primarily in the research realm; development of this technology will no doubt greatly accelerate clinical translation.
While science has been slow to recognize the impact of gene expression on psychosocial behavior, there has been significant development in several key areas—psychogenomics, social genomics, and cognitive genomics.
The recently-introduced area of psychogenomics explores the genomic and molecular underpinnings of normal and abnormal behavior, along with disorders of the brain, such as addiction and depression, to develop better diagnostic tools, preventive measures, and treatments. Currently available genomic testing addresses these areas and provides valuable information for clinicians in practice today.
In contrast, social genomics examines why and how different social factors and processes—such as social stress, conflict, isolation, attachment, rejection—affect the expression of individual genes or clusters of multiple genes. While the direct application of testing is not yet available, understanding and applying some of these general principles is spurring more research in community-focused practices.
Lastly, cognitive genomics studies how changes in cognitive processes are associated with gene profiles, especially as it relates to neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, which are estimated to affect more than 15 million Americans by the year 2030. It is clear that the clinical genomic applications are expanding in parallel with scientific advances to better understand the underlying biological systems and causes of these devastating neurodegenerative diseases.
Nutritional genomic, pharmacogenomic, and microbiome testing are readily available for clinicians to use today in their practices. Functional and integrative practitioners are often uniquely equipped to integrate these new tools. There are many commercial labs that provide a range of testing and interpretation services. The challenge for practitioners is to understand the benefits and limitations of each, and how best to integrate the findings into their current practice model. We believe establishing a partnership with testing laboratories is essential, since they can provide the types of services and support for your specific needs.
Start with testing on yourself and then build on what you have learned at a pace that is comfortable. We have found that practitioners who follow these steps can successfully implement personalized genomic medicine in their practices within a fairly short period of time.
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About the Authors
Dr. Roberta Kline and Dr. Joe Veltmann have extensive experience in conventional, functional and integrative medicine, with over 20 years combined experience using genomic medicine in clinical practice. They are cofounders of Genoma International, offering comprehensive genomic testing and genomic medicine education to clinicians. They also offer personalized genomic medicine consulting to patients worldwide through their practice, the GENESIS Center for Personalized Health.