Genetic, methylation and epigenetic testing: what each one tells you

Genetic testing reads your DNA sequence, the code you were born with. It does not change over your life.

Methylation, in a lab report, usually refers to a set of chemical reactions that depend on folate, vitamin B12, vitamin B6 and related nutrients. Markers such as homocysteine show how well those reactions are running right now, and they can change with diet, supplements and health.

Epigenetic testing looks at chemical tags on your DNA, mainly methyl groups, that switch genes on and off. Those tags shift with age and environment. Epigenetic age tests use patterns in them to estimate biological age.

MTHFR is a gene that makes an enzyme involved in processing folate. Common variants in it are widespread, and many people have one or two copies. MedlinePlus explains that some variants reduce the enzyme's activity and can raise homocysteine, especially when folate intake is low.

Here is the part that often gets lost online. The American College of Medical Genetics and Genomics recommends against ordering MTHFR variant testing to assess clotting risk or recurrent pregnancy loss, because the variants alone have not proven useful for those decisions. Measuring homocysteine and the relevant vitamins usually tells you more about what is happening than the gene result does.

In 2013, researcher Steve Horvath showed that DNA methylation patterns across many tissues track closely with chronological age. That work led to a family of epigenetic clocks. Commercial tests such as TruAge build on this research to estimate how old your body appears at a molecular level.

These tests are interesting for tracking change over time under the same test. They are estimates, they are not diagnostic, and results from different companies are not directly comparable.

Clinicians commonly assess methylation with blood markers such as homocysteine, folate and vitamin B12, sometimes alongside genetic variants in genes like MTHFR. The blood markers tell you how the system is working now. Gene variants tell you about tendencies you were born with. When the two disagree, the current blood markers are usually the better guide for decisions about diet and supplements.

A methylation assessment is often useful for people with a family history of heart disease, those following restricted diets such as vegan eating, and anyone with low or borderline B12 or folate on routine labs. Epigenetic age testing appeals to people who like to track change over time and want one more number to compare before and after a period of focused work on sleep, training or nutrition.

For most people, neither test is the first place to start. Core bloodwork usually answers more questions per dollar, and these tests add depth once the basics are covered.

Most common gene variants have a small effect on their own. Traits like heart health, weight and energy are shaped by many genes working together with sleep, diet, activity, stress and environment. A single variant rarely decides an outcome, and two people with the same result can have very different health.

That is why professional guidelines are cautious. The American College of Medical Genetics and Genomics advises against ordering MTHFR testing to assess risk for blood clots or recurrent pregnancy loss, because the common variants have not been shown to change outcomes in those settings. For most people, measured markers such as homocysteine, folate and B12 levels say more about how the body is handling these pathways today than the gene result does.

Epigenetic age tests are also still being validated. Results can shift between labs and between repeat tests, so they are most useful as one trend line read alongside standard labs over time.

Genetic results are personal, permanent and shared in part with your relatives. In the United States, the Genetic Information Nondiscrimination Act protects against genetic discrimination in health insurance and most employment. It does not cover life, disability or long-term care insurance. If you are considering a consumer DNA test, read how the company stores and shares data before you send anything.

The FDA reviews some direct-to-consumer genetic tests and warns that results should not be used to make medical decisions without a health care provider. Our view is similar. A result is useful when someone who knows your history explains it and it changes what you do next.

At LYV, our advanced testing menu includes a methylation panel and the TruAge epigenetic age test. Complete Insight members get a methylation test each year as part of their functional testing. A provider reviews every result with you and puts the useful parts into a written plan.