What is a genetic test?

As described in the previous blog post, the human genome consists of 46 chromosomes made up of DNA. Genes are specific sequences within this DNA that contain instructions for building the molecules that function in our bodies. DNA has variable sites, meaning that your genes are not necessarily identical to mine. Most of this variation is harmless and appears in traits such as eye or hair colour. Some variation, however, can influence disease risk, and identifying such variation can be useful.

So, what is a genetic test?

In short, a genetic test is a laboratory analysis in which the DNA sequence of a person – or any other creature* – is examined at specific locations in the genome. The identified sequence is compared with reference data in databases, allowing genetic variants to be detected and their potential effects on disease risk or other traits to be evaluated. Genetic tests therefore do not typically examine the entire genome but instead focus on specific genes and variants known to be associated with a particular disease or other characteristic.

*) Genetic tests are available not only for humans, but also for pets!

How is a genetic test carried out?

A genetic test is usually performed using a blood or saliva sample. This can be collected in a healthcare setting, but in some cases, it can also be taken at home and sent to a laboratory for analysis. DNA is then extracted from the sample.

Typically, the DNA is first amplified using the polymerase chain reaction (PCR) to obtain enough material for actual testing. Genetic variants can then be identified using several different methods, depending on the laboratory and the type of test. One approach is to use microarrays, which can simultaneously detect a large number of known variants. Sequencing methods are also widely used, allowing the DNA sequence to be read more directly and more broadly than just for the known variants.

When is a genetic test useful?

In healthcare, genetic tests are used particularly when a hereditary disease is suspected. If a family has a history of, for example, cancer, heart disease, or a rare inherited condition, genetic testing can help to clarify the biological basis of the disease.

In some cases, genetic information can also support prevention: if a person is found to carry a variant associated with increased disease risk, their health can be monitored more closely or preventive measures may be considered, such as a mastectomy in individuals found to carry a breast cancer-causing variant in the BRCA1 or BRCA2 gene.

Genetic information can also inform drug treatment. Certain genetic variants affect how the body responds to medications; this specialized field of genetic research is called pharmacogenetics. The dosing of the blood-thinning medication warfarin, for example, has traditionally required careful monitoring and adjustment. Today, a pharmacogenetic testing can be used to examine variants in genes such as CYP2C9 and VKORC1, which influence how quickly warfarin is metabolized. Based on this information, a more appropriate starting dose can be selected.

Where do the headaches come from?

Some human diseases are monogenic, meaning that the disease mechanism can be attributed to a variant in a single gene. In Finland, we have the Finnish disease heritage, a group of 36 rare diseases that are more common among Finns than other populations. For diseases of this kind, and other single-gene traits, genetic testing is not only technically straightforward but also meaningful from the patient’s perspective.

Most common diseases, such as heart disease, type 2 diabetes, or Alzheimer’s disease, are multifactorial. This means that their development is influenced by multiple genes as well as non-genetic factors, such as lifestyle. In these conditions, the effect of any single genetic variant is often small, and the same variant may be present in many healthy individuals.

Alzheimer’s disease and the APOE gene provide a well-known example. APOE has three common forms, e2, e3 ja e4. The e4 form is associated with a substantially higher Alzheimer’s disease risk, and individuals carrying two copies may have up to 12 times higher risk compared to those carrying two copies of the e3 form. Yet many e4 carriers never develop Alzheimer’s disease, and conversely, many individuals develop the disease without carrying this variant.

This complexity makes genetic test results difficult to interpret: identifying a risk variant does not mean that a person will necessarily develop a disease, and a negative result does not rule it out. Furthermore, our understanding of the effects of many genetic variants remains incomplete. Direct-to-consumer genetic tests are therefore particularly tricky: results that report on numerous genetic variants and their relative risks can cause unnecessary concern or, conversely, give a misleading sense of reassurance. Even for professionals, interpretation can be difficult.

To conclude

Although the results of direct-to-consumer genetic tests should be interpreted with caution, they can increase interest in one’s own genome and health. Not all such tests focus on disease; they can also provide insights into ancestry and genetic background. Genetic research and our understanding of test results are continuously evolving, and in the future, improved interpretation of genomic information may offer new opportunities for both research and healthcare.

Author

Eeva Sliz