Information for insurance & underwriting providers

Epigenetics is a rapidly growing field in molecular biology that aims to understand how gene expression – i.e., whether a gene is turned “off” or “on” – is affected by changes unrelated to the changes in the underlying DNA sequence. As described by the researcher Conrad Waddington in 1942, the basic question for epigenetics was to investigate how a given cell could differentiate itself as a certain type of cell, given that all cells contain the same DNA. The idea that a cell’s fate might be controlled by other, external factors, besides the DNA sequence itself, has been and remains the fundamental premise of epigenetics.

Today, epigenetic science is part of a host of biotechnology tools helping transform healthcare into modern precision medicine. These industry tools also offer exciting opportunities to modernize underwriting, with direct application in healthcare such as life and long-term care insurance.

So epigenetics is about how genes are expressed and used, rather than the DNA sequence of the genes themselves, but how does this work? We know that a part of how epigenetics works is by adding and removing small chemical tags to DNA. You can think of these tags as post-it notes that highlight particular genes with information about whether they should be switched on or off. In fact the chemical tag in question is called a methyl group and it is used to modify one of the four bases or “chemical letters”, A, C, T and G, that makes up the genetic code of our DNA. These base pairs comprise the double helix structure of DNA that composes our chromosomes. The order, or sequence, of these base pairs provides the blueprint for biological life.

The letter that is tagged is C or cytosine and when it is modified, or methylated it is called 5-methyl cytosine. Methyl groups are added to DNA by enzymes called DNA methyl transferases (DNMTs). Today, it is understood that mechanisms of DNA methylation are central to both normal cellular development and function, as well as dysfunction and disease development. Most important, that they can leave distinct patterns along the epigenome that can be tied back to factors such as age, health status, disease status, and even behaviors (e.g., smoking, exercise, diet, chemical exposure, and drug use).

The trajectory behind epigenetic science and technology is closely tied to the recent advancement of biotechnology. Up until the early 2000’s, relatively little had been done to study epigenetics. Epigenetic research on a widespread basis was enabled by the commercialization of micro-array and “next-generation” sequencing technologies and bioinformatic methodologies, which have matured in terms of cost effectiveness and adoption.

Today, the human genome can be sequenced at a cost of less than $1,000, with “next-generation” or “second generation” sequencing allowing the study of molecular health in ways that were inconceivable a decade earlier. Emerging in the 1990s and becoming commercially available in the 2000s, these “massive parallel sequencing” approaches, as well as tools such as micro-arrays, have opened up a vast area of genetic and epigenetic research due to their ability to scan millions and billions of base pairs at a time. These tools have enabled vast research into patterns of DNA sequences and DNA methylation that differ between normal and diseased states and have yielded an abundance of peer-reviewed, scientific studies called genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS).

In today’s world of “Big Data,” the importance of artificial intelligence and machine learning on molecular research cannot be overstated. The availability of large-scale computing, new algorithms and bioinformatic techniques allow for troves of biological data produced by next-generation sequencing and micro-arrays to be analyzed to find existing molecular markers (“biomarkers”) associated with health and disease, as well as predict future disease risk. New innovations are being rapidly developed to understand whether and how DNA methylation and other epigenetic changes offer insights into the diagnosis and treatment of diseases, including cancer, neurological disorders, heart failure, Alzheimer’s, and aging itself.

The full potential understanding of molecular biology and epigenetic mechanisms in health and disease has yet to be fully realized.

There is a widely recognized framework for evaluating clinical tests which can be applied to evaluating epigenetic tests. This evaluation framework is comprised of three key headings: analytical validity, clinical validity, and clinical utility:

• Analytical validity refers to how well the test predicts the presence or absence of a particular epigenetic change. In other words, can the test accurately detect whether a specific epigenetic variant is present or absent?
• Clinical validity refers to how well the epigenetic variant(s) being analyzed is related to the presence, absence, or risk of a specific disease.
• Clinical utility refers to whether the test can provide information about diagnosis, treatment, management, or prevention of a disease that will be helpful to a consumer.

The analytical validity of a test is often assessed with gold standard measures. Gold standards, however, must be appropriate to the purpose of an epigenetic test. For instance, when a direct measure is needed to determine methylation levels at specific epigenetic sites, bisulfite sequencing is generally considered the gold standard.

For a laboratory to establish clinical validity for a DNA methylation test, it must establish performance characteristics that include an analysis of accuracy, precision, analytical sensitivity, analytical specificity, reportable range, reference interval, and any other performance characteristics required for the test system in the laboratory that intends to use it.

While analytical validity involves comparing the test output to a reference standard, clinical validity involves comparison of the processed test result with the clinical disease or trait that it seeks to detect.

Epigenetic testing has only started to be explored for life insurance underwriting, but its advocates believe it to be a tool that holds promise to pave the way for more precise underwriting and more personalized life insurance premiums. According to a report from industry research firm, Capgemini, the key drivers for the adoption of epigenetics include speeding up insurance delivery, enhancing the customer journey with non-invasive testing, and developing innovative life insurance products.

Like traditional medical check-up, epigenetic tests require access to a biological specimen. 

If blood is used to derive epigenetic information, then the specimens could simply be collected through existing medical procedures currently used in fully underwritten cases (only for EU area).

One benefit that epigenetic testing may provide over traditional methods is the opportunity to use saliva rather than blood to glean applicant health information. Saliva specimens may provide sufficient epigenetic information to meaningfully enhance accelerated underwriting. A saliva specimen could be collected in a variety of ways, such as by an agent, notary, paramedical technician, retail pharmacy, or self-collected by the consumer, as is currently done for direct-to-consumer epigenetic tests. Saliva has the advantage of being easily shipped through regular mail, which may be useful in situations where medical services are unavailable. This approach could improve turnaround times in a noninvasive manner, while providing information that could fully substitute for traditional lab screens.

The top ten areas studied in epigenetic studies reported to the National Genomic Data Centers are:

• Analysis of biological age
• Underwriting risk classifications
• Tobacco risk assessment
• Alcohol consumption
• Type 2 Diabetes
• Colon and breast cancer screening tests
• Cardiovascular disorders
• Depression
• Environmental exposures
• Radiation exposure

For each of these areas of health, disease, and behaviors, as well as others, epigenetic biomarkers and diagnostics sets are developed to test an individual applicant for the presence or absence of a given trait. Since a substantial body of epigenetics research seeks to understand the behaviors and risk factors associated with “lifestyle diseases” and its resulting impact on aging, much epigenetic research has direct application to the medical underwriting of risk factors.

Up to the present, the early commercialization of epigenetic tests for life underwriting has focused on the areas of smoking and alcohol consumption, aging, diabetes, and cancer screening tests.

Currently, we are gaining market-share and new strategic partners, scientific education, growth within existing direct-to-consumer channels and opening new markets.

We are interested on discovery and further integration of epigenetics technology into a next-generation underwriting protocol and consumer engagement platform that uses epigenetic biomarkers to assess individual health and wellness.