Marketing ploy in genetic testing?

How do genetic tests actually work, what are they used for, and is it worth believing in the “DNA-based diet” advertisements?

Direct-to-consumer genetic tests have become very popular and are actively advertised. Biologists, doctors, and medical geneticists discuss such tests but rarely publish materials on this topic that are accessible to a wide audience. Clinical bioinformatics in the field of medical genetics, explains who needs genetic tests, when they are useless, and how to distinguish dubious recommendations of such tests from harmless ones.

What is a genetic mutation?

The diversity of living organisms, including humans, is partly (though not entirely) due to the diversity of their genomes.

At first approximation, the genome can be considered a text composed of four letters (nucleotide residues). All genomes on Earth change over time, inevitably. When a stable change occurs in the DNA sequence (roughly speaking, one letter in its text is replaced with another, some letters are dropped, rearranged, or new fragments are inserted into the text) and such change is inherited in a number of generations, genetics say that a mutation has occurred.

The word ‘mutation’ scares many people, but there’s nothing to be afraid of: if there were no mutations, there would be no diversity of life, no evolution; we are all genetically different from each other and all new DNA variants arise as a result of mutations, which are then inherited by descendants.

According to one of the recent studies, the average human genome differs from the reference sequence (a “sample”, not an “ideal” that doesn’t exist) by 4-5 million positions. At the same time, 2-2.5 thousand differences are not single-point changes in one “letter” but rather larger variations, such as insertions and deletions of many “letters” at once. Due to this complexity, on average the number of differing letters is 20 million! The number of differences between two people depends heavily on the population: the most genetically diverse people are in Africa, where our species originated and from where Homo sapiens spread to other continents.

There are mutations that affect large fragments of the genome, such as variations in the number of chromosomes, each of which can contain hundreds of genes. One example of such mutations is trisomy of the 21st chromosome, associated with Down syndrome. Trisomies occur as a result of the abnormal separation of chromosomes during the formation of sex cells, and the risk of such abnormalities increases with the mother’s age. It is impossible to fully protect against it, however, pregnant women can undergo a non-invasive prenatal test (NIPT), which detects chromosomal abnormalities in the fetus’s DNA, circulating in the mother’s blood, as early as the 10th week of pregnancy. By the way, with the father’s age, the risk of point mutations increases much more than with the mother’s age, so there is a sort of parity here (each of the sexes contributes more and more to their own sort of mutations as they age).

It should be noted that some deviations from the normal chromosomal set do not cause significant problems – for example, according to some data, 1 in 500 to 1 in 1000 men have the XXY sex chromosome set instead of XY, and many of them do not know about it. Carrying such a genotype can be asymptomatic, although it may manifest as reduced fertility, gynecomastia, and some other problems. Women with the XXX set may also not have any symptoms.

When discussing the benefits of genetic testing, we will mainly be talking about gene mutations that affect relatively small sections of DNA.

Recessive mutations: What does “lucky with genes” mean?

Most genetic differences between people are neutral or nearly neutral, meaning they don’t harm much, although they don’t bring any benefits. The reason is that most mutations fall into intergenic regions with unknown functions to scientists at the moment: they are believed to have little impact on genome function, although there are many exceptions.

Even mutations affecting the coding part of genes often have little or no effect on their functions. If a mutation in the genome manifests as a change in some trait, this change is not necessarily harmful. For example, the existence of different blood groups doesn’t affect the survival and reproduction of individuals.

In discussions of human genetic diversity, the concept of “neutral polymorphism” or “neutral variation” is used: it means that the genomes of all people differ, but these differences are not necessarily bad or harmful.

There are many harmful mutations that do not manifest in an organism because it has a second copy of the gene – after all, during sexual reproduction, we receive one copy of most genes from our mother and one from our father (with the exception of sex chromosomes and mitochondrial DNA, which are slightly more complex).

Such mutations, which do not manifest if only one of the two gene copies that we have is affected, are called recessive. Harmful recessive mutations are present in the genome of each of us in large numbers: there are no “genetic angels” among us with perfect DNA, not carrying any “breaks” (although the concept of a “break” is also a simplification) – they simply cannot exist.

Luck is not when there are no “breaks” in the genome, but when these “breaks” are in different genes in our parents. When defective copies of the same gene are present in both parents, a so-called monogenic (dependent on one gene) disease may occur in the child.

Not all genes are associated with known monogenic diseases. The OMIM medical-genetic database currently contains around 3,700 genes associated with certain diseases, while a human has around 20,000 protein-coding genes and approximately the same number of non-protein coding genes (estimates vary as usual). Of course, our knowledge is incomplete: scientists and doctors continue to discover new links between genes and diseases.

Mutations as chance: nobody is to blame

Unlike recessive, dominant mutations are expressed even if they are present in only one copy of the gene. Some of these dominant variants, causing genetic diseases, arise de novo, meaning that neither the father nor the mother was a carrier of this mutation, but it arose at some stage in the formation of sex cells or the embryo and is expressed in the child.

Pathogenic de novo mutations, like others, occur rarely but it is impossible to fully protect against them as their occurrence is a random process where nobody can be blamed. Studies of parents and children revealed that each person has on average about 60 new mutations (including point variants and insertions-deletions) but most of them do not cause serious disruptions.

The mutation process cannot be stopped, it can only be slowed down by reducing the impact of external mutagenic factors. However, such internal causes of mutations, such as DNA copying errors, cannot be eliminated.

Mutagenic and carcinogenic factors are not exactly the same, but the nuances cannot be considered here. It is important to note that mutations can lead to cancer (and other problems) – but they don’t necessarily lead.

There are also somatic mutations – they occur during the division of body cells and are present only in some tissues of the organism (and not in sexual cells). They can also be neutral – but many somatic mutations are associated with diseases: for example, many somatic mutations occur in cancer.

One of the well-studied mutagenic factors that we all face is ultraviolet radiation. It has been shown to cause the formation of dimers (thymine dimers) in DNA and as a result, increases the frequency of skin cancer. Another mutagenic factor is human papillomavirus (dangerous oncogenic subtypes), which integrates into the genome. However, these factors affect body cells (skin or epithelia of reproductive organs), not embryonic cells.

Sexual cells can be affected by, for example, a level of radioactive radiation significantly exceeding the background, some chemical substances (but not those usually thought of). In particular, mutagenic and carcinogenic substances are contained in smoke, including cigarette smoke (although they also affect the respiratory organs to a greater extent).

In all these cases, the dose of the substance or exposure is important, as the body has protective systems that constantly “repair” DNA: with some level of exposure, they cope, and it does not cause a significant increase in the frequency of mutations.

Useful Mutations

But not all mutations are “bad” or “useless”. There are also useful mutations that increase the adaptability of organisms—ultimately, without them, the evolution of new forms of life would not be possible.

Thus, the famous CCR5-Δ32 mutation, which Chinese scientist He Jiankui (allegedly) inserted into the genomes of two girls with limited success, is present in human populations and significantly reduces the risk of HIV infection (if present in both copies of the gene—according to available data, almost to zero). This example shows that the “usefulness” of genetic variants depends on conditions: before the spread of HIV in human populations, this variant could have been neutral or even slightly harmful, but now everything has changed!

Clinical geneticists typically use the term “genetic variant” or simply “variant” instead of “mutation”, as the term is free of negative connotations, although all genetic variants arise as a result of the mutational process. When studying the genome, the primary focus is on how a specific “version” of the genetic text is associated with organism traits and what risks certain genetic variants may carry.

There is a common practice among geneticists to label variants with a population frequency less than 1% as mutations, and those with a frequency higher than 1% as polymorphisms (i.e., “normal” variants), but this boundary is arbitrary.

Types of genetic tests

Firstly, they differ in technology:

1. PCR. They examine a set of specific DNA segments, for example, they check for the presence of certain known genetic variants in a person. But with this method, you can only see a relatively small number of variants: if you want to see many at once, it is cheaper to do it with other methods.
2. Microchips. These are glasses that have DNA fragments “sewn” onto them, which specifically “stick” to the samples being studied, allowing us to determine if a specific variant is present in the sample or not. Chips can detect tens or even hundreds of thousands of variants and are used by many well-known genetic companies widely known to the public.
3. Various sequencing technologies. These are ways of directly reading the genetic text. The “classical” Sanger sequencing has existed since 1977 and allows us to read, as a rule, within a thousand nucleotides “at a time” (this is several times less than the size of an average gene). Despite this, such sequencing method is still widely used and is the “gold standard” for detecting some genetic variants.
4. NGS (Next Generation Sequencing), also known as high-performance sequencing technologies, is a “umbrella” term. These methods allow for the reading of most sections of a human genome in one “run” (excluding “problematic” areas such as short sequences that are repeated many times). NGS can also only read the exome, which is the coding part of the genome (approximately 1% of the full genome), and is significantly cheaper. This part of the genome is also better studied than the non-coding part, therefore, it provides more useful information.
5. Chromosomal microarray analysis, MLPA, and PCR-based methods can be used to study large structural rearrangements (duplications, deletions, insertions, transfers of fragments from one chromosome to another chromosome), which affect extended regions of the genome. Many human diseases are related to these rearrangements.
6. Karyotyping. It is the study of the “appearance” of chromosomes in dividing cells. It reveals deviations from the normal number of chromosomes, such as trisomy 21 in Down syndrome.

It is important to remember that even NGS genome or exome sequencing – although considered the most advanced method today – may not always be able to detect certain potentially harmful variants due to technology limitations. In our population, the frequency of spinal muscular atrophy (SMA) carriers is quite high, with severe forms leading to death or disability. Approximately every 36th or 37th person in Russia is a carrier of SMA. A test for SMA carrier status can be recommended to all those planning a pregnancy and is performed using a special methodology.

A well-selected (ideally by a geneticist) test can bring many benefits. For example, there is no doubt about the usefulness of testing for carrier status of pathogenic mutations before pregnancy, as well as examining so-called recommended secondary findings, which are genetic variants that significantly increase the risk of certain diseases (such as cardiovascular or oncological) and this risk can be reduced with certain preventive measures. These genetic variants are mainly rare, but this does not mean that checking for their presence is meaningless.

Consumer genetic testing

The testing method should be chosen based on your goal: taking into account the limitations that exist with any technology, and evaluating which method is best suited to answer the question asked. To do this, you obviously need to formulate the question yourself. In a clinic, this is dealt with by a geneticist doctor: he understands the advantages and disadvantages of methods and knows what needs to be specifically checked for the person based on clinical data, family history, and medical history.

There are also what are called Direct to Consumer (DTC) genetic tests – those same kits with saliva samples that are sold directly to users who want to learn something about their genome. Doctor’s involvement is not expected in this case. The target audience of such tests is generally healthy people who do not see a particular reason to go to a genetic doctor for a check-up.

DTC companies offer origin analysis, dietary and sports recommendations, etc. They have become commercially successful for a number of reasons:

1. Interest of investors and the general public in the rapid development of genetic technologies;
2. Adroit marketing and good design (knowing the “sensitive points” of your customer to target, for example, a parent’s concern for their child’s future, beautiful modern websites, well-designed brochures with results, texts written by professional copywriters, etc.);
3. The eternal desire of man to explore himself;
4. Fashionable trends: wellness and fitness, increased productivity, “smart” approaches to sports and beauty, various biohacking.

However, this does not mean that the results of relevant tests necessarily improve people’s lives (besides causing interest and dispelling boredom).

Issues surrounding genetic testing: big data, ethics and futility.

DTC tests bring more benefits to scientists than to the buyers of the tests themselves. Some people upload their genetic data to websites like GEDMatch and find relatives – this is generally considered good, for example, people want to find relatives. The police catch the “Golden State Killer” with the help of GEDMatch – also good. Someone starts eating better or exercising because the test results showed a high risk of diabetes or atherosclerosis – also generally good (even regardless of the scientific validity of the assumption that this is more beneficial for them than for someone else).

However, many also talk about potential harm: there is a high risk of information leak to third parties that you wouldn’t want to trust with your information such as insurance companies and big data collectors like the ones Facebook collaborates with.

Additionally, there is a risk of falling into depression due to discovering ‘bad’ options, etc.

The community of clinical geneticists widely discusses various ethical aspects of genetic technology, including the right not to know – a person’s right not to receive certain information about themselves (which can sometimes be problematic, for example, when specialists are examining a child but are not supposed to reveal certain information about the parents).

The concept of informed consent is significant here: for someone to give it, they must understand what they are agreeing to — for example, are they willing to find out that they have a high risk of a disease that will manifest later and cannot be prevented or cured?

It is true that the more information scientists gather about genetic variation and its relationship with traits, the more useful genetic tests of the future will become. The potential value of a test depends on the size of the existing database used to interpret the results. Hence, the positive effect of accumulating genetic big data is generally inevitable.

In this sense, although scientists complain about DTC tests, they use their results (if users consent to the use of their anonymous information in scientific research and if the company decides to disclose some data obtained).

However, for the use of DTC genetic test data in science, clinically significant information about users is often not enough. There are scientific projects that systematically collect such information, but donors do not pay for the test.

How do consumer genetic tests work

Most companies in the market (23&me, etc.) offer microchip analysis that allows you to view tens of thousands of genetic variations, and some even offer full genome or exome sequencing (the coding part of the genome: about 3 million nucleotide positions, each of which can exist in one or two variants at the same time).

Some companies only analyze a few tens of SNPs (single nucleotide polymorphisms), variations that affect a specific “letter” of the genetic “text”. They work by PCR method and claim that more analysis is simply “not needed” – but you will see that problems begin when trying to understand why it is all “needed.

Such companies do not offer ancestry analysis: they simply do not have the raw data for this. And this, if we leave aside the question of the necessity of such analysis and the problem of interpreting its results: the same 23&me (and many other companies) offer ancestry analysis, although population genetics do not consider their interpretation to be entirely correct.

The main question that arises with such results is the question of the validity of the connection between the genome or variant and a certain state or disease, as well as a certain recommendation.

This question is answered every day by a clinical geneticist or bioinformatician when it comes to mutations related to inherited diseases.

If you think about the test in terms of the raw data it provides, which will not change throughout your life and can be reanalyzed multiple times, then the test should be selected based on the amount of high-quality “snips” it can detect for the least amount of money. The interpretation can always be done independently, using third-party services or by consulting other companies.

For an independent evaluation, it’s important to find out beforehand in what form you will receive your data and what you can do with it afterwards. Most likely, it will be a list of detected “snips” that you won’t understand. What the user really wants is a design brochure with interpretation, although in reality, this is the least significant result of a DTC test.

In medical genetics, a clinical conclusion is given, which can be discussed with the directing geneticist doctor. It is better to find out about the quality of the user test data beforehand: if it is qualitative data, it can be beneficial. It cannot be excluded that many years will pass, and these data will turn out to be much more useful than today, and will open up space for additional (scientifically conscientious!) interpretation.

True, after many years, genetic testing technologies will become much cheaper: this is happening constantly – often it is said that the cheapening of genetic technologies has surpassed Moore’s law.

But ultimately, all this only matters if you understand why you are doing the test and what questions you want to answer.

Genetic testing in hereditary diseases

In the case of monogenic (i.e. caused by mutations in a specific gene) hereditary disease, there are clear criteria according to which all genetic variants (i.e. differences from the “reference” DNA sequence) are divided into five classes:

• Pathogenic
• Likely pathogenic
• Benign
• Likely benign
• Uncertain significance

These criteria are formulated by the American College of Medical Genetics and Genomics and the Association of Molecular Pathology, and virtually all genetic laboratories and companies worldwide refer to these recommendations in their materials, but not always correctly applied. There are also more specialized international recommendations regarding specific diseases.

Strictly speaking, these recommendations are not applicable to the genome research of healthy people without medical indications for genetic testing. However, the general principles of information analysis remain the same.

In the case of polygenic and multifactorial diseases – that is, those dependent on multiple genes and largely on the environment, such as type 2 diabetes or many mental health diseases – the situation is more complex. There is no such clear link between mutation and disease: a risk is determined, which increases or decreases depending on certain genetic conditions.

In this case, it is important to know what methodology was used and based on what the calculation was made and how much your risk has changed compared to the average for the population.

The contribution of each individual gene and mutation to the risk of such multifactorial diseases is usually very small — and the impact of environmental factors more than compensates for the contribution of a specific mutation.

For example, if we’re talking about type 2 diabetes, changing your diet and lifestyle can significantly reduce your risk. But you already know this, so why do you need a test? Testing for hereditary forms of diabetes can be recommended by a geneticist if there is a family history of the disease.

When genetic tests are needed for healthy people

In clinical genetics, there is a list of secondary findings that we are obligated to inform the person of regardless of medical indications for the test. These are known pathogenic or expectedly pathogenic mutations in genes predisposing to cancer, genes affecting cardio risk and causing dangerous cardiovascular diseases that may occur almost asymptomatically, and some others.

Why are these genes singled out among others? Because the result we get is called actionable: we know what specific actions need to be taken to prevent the development of the disease or cure it if it has already arisen, and the effectiveness of these actions has been proven.

Everyone knows about Angelina Jolie’s story: it’s a clear example of how it happens. Sometimes people undergo preventative mastectomy based on genetic test results, and a histological analysis reveals that there was already an early stage of cancer that was not detected by any other methods.

Scary? But this is exactly what a genetic test looks like, one that can actually save your life.

The debates about whether to screen the entire healthy population for such mutations among medical genetics community persist. Partly, these debates concern the effectiveness of detecting these diseases in the healthcare system: if a person is examined for their own money, I would recommend that they investigate these genes in themselves and their children, if they are prepared to accept negative results, which will be confirmed in informed consent. This is really important.

The same group includes malignant hyperthermia, a rare inherited condition in which a person cannot tolerate some common anesthetics for general anesthesia. As a result of anesthesia, a person with a mutation in a certain gene falls into a serious condition and can even die. The drug dantrolene, which still needs to be urgently found (it is not available in all hospitals), can save them.

But the companies discussed, which produce DTC genetic tests, are not betting on such cases at all. Of course: people are frightened by it, it is hard to talk about it, and only doctors can take responsibility for communicating such results and further actions.

Exceptions are made by companies that specifically study genes for hereditary predisposition to cancer. However, in general, companies selling DTC genetic tests do not advertise in their advertisements the possibility of finding such life-important information – because their product is closer to the entertainment cosmetology industry than to medicine.

User genetic test recommendations: meaningless, universally useful, and questionable.

Meaningless and harmless

Meaningless recommendations are usually harmless: potentially harmful recommendations are still feared in order to avoid responsibility for consequences. At the same time, we know that many truly effective interventions, including drug prescriptions, carry risks—and it’s the doctor’s job to weigh the risk/benefit ratio in your specific case.

For example, there’s no need to complicate your life and increase expenses by going on a gluten-free diet if you actually have no gluten intolerance, even though it may not harm your health. You can’t be prohibited from doing it if you want to.

The purchase of certain creams or physical exercises – no one and never will be able to verify if these recommendations worked in your case or not. And this means that no one can claim against the company that gave you these recommendations because we don’t have anything to compare with and we don’t know what would have happened to you if you hadn’t bought the cream or started doing the exercise.

How can this really be determined? By conducting large-scale studies comparing people who use the cream or exercise with those who do not. For drugs, such studies are mandatory, but for non-drug interventions, they are not (although the effectiveness of non-drug interventions such as diet and physical exercise for many diseases is actively studied). Studies on creams and exercises, if conducted, are usually conducted on “people in general,” not carriers of a specific mutation. In this way, at best, you know that the effect works (or not). Not with the mutation, but in principle.

Then why the test? The result of your test is not likely to be related to the effectiveness of the cream or exercise.

Universally useful regardless of genotype

Consuming less sugar, eating more fruits, vegetables, and fiber-rich products, moving more, not smoking, reducing caloric intake if excessive, all of these are things from the WHO website / textbook. They are suitable for all people and there is no need to do genetic tests to follow them.

Each chapter of a test result is usually accompanied by references to scientific publications. This looks weighty and irrefutable, but it is important to find out what is written in these articles, who, when, what was researched and by what methods. It is possible that established patterns have a very indirect relationship to your situation or do not allow for any specific recommendations.

If a genetic variant is frequently found in a healthy population, this is already a serious basis for considering the variant to be harmless. However, some DTC companies describe relatively frequent (and even proven neutral) variants as having some negative effects, although there is no basis for this.

Yes, sometimes articles can be found about the negative impact of this variant – therefore, you will be presented with a link to a scientific source. But either these articles are old and have already been debunked, or they are made on insufficiently large samples of subjects or for some other reason do not allow a definitive conclusion about the connection between the mutation and the disease.

In general, such frequent variants are simply polymorphisms, a neutral variation: for example, many variants of hair or eye color are found in people, but none of them is better or worse, the same applies to other traits.

There is even a phenomenon of “speculation on polymorphisms”: for those who have harmless variants of folic acid cycle genes discovered, commercial companies that produce genetic tests prescribe dietary supplements containing methylfolates – and sometimes even provide a promo code for purchasing these methylfolates on a certain website or company, to get a percentage of the sales. The dietary supplement is not a medicine and the person recommending it is not a doctor, so neither the author of the recommendation nor the seller bear any responsibility for the result of taking these substances.

Doubtful

The recommendations you receive from taking a consumer genetic test are often not based on any scientific or clinical consensus.

Individual articles cited as references cannot serve as a basis for recommendations. Furthermore, these recommendations are usually never tested on carriers of relevant genetic variations, or if tested, a verdict was pronounced on the lack of basis for different recommendations in case of mutation carriers and its absence.

For example, a study on personalized diets in 2016 showed no impact of considering genotype information in the creation of an individual diet on the health outcomes of participants.

In this study, no connection was shown between genotype and diet efficiency. Yet personalized diet is one of the most popular products of “entertainment” genetic tests! Scientists regularly release studies that show that the recommendations of DTC genetic tests lack scientific basis. The American Academy of Nutrition and Dietetics in 2014 clearly did not recommend undergoing commercial nutrigenomic tests due to the lack of sufficient evidence. The Australian Sports Institute released a consensus statement in which it declared that at the moment there is no sense in conducting genetic testing to predict success in sports, choose a sport discipline, or select talent.

Outrageous recommendations from consumer genetic tests: cosmetic speculations

The creators of some widely advertised tests determine the presence of mutations in collagen and elastin genes. In the brochures with the results of the genetic test, clients may be offered such cosmetic procedures as mesotherapy, hyaluronic acid biorevitalization, glycolic peeling, facial massage, or organic silicon injections.

Organic silicon injections, seriously? What is organic silicon from a chemical point of view? Of course, it is just a market name for some silicon preparation with unknown efficacy. It has nothing to do with silicic organic chemistry, which is known only to those who are familiar with chemistry. The only known silicic organic compound that is used in biological systems is a poison, a pesticide (there are such drug developments, but none of them is used yet). Si-C bonds in biological systems do not occur in normal circumstances. Such a “miracle” significantly reduces trust and to all other materials.

Leaving aside the huge problem of proof and scientific justification of cosmetics as such – this is a separate topic for scientists to be outraged about.

But are there studies that confirm that it is precisely these mutations in the collagen type I gene that significantly improve the skin condition and specifically show mesotherapy to carriers of such mutations earlier/more often than others? No, you will not find such articles. Perhaps this question has been studied in some studies, but it was definitely not the main focus: there is not a single article in the PubMed database that can be found under the query mesotherapy + variant or mutation.

The query mesotherapy + genetic brings up two articles about bacterial infections that occurred as a result of mesotherapy, and genetics were used there to identify pathogenic microorganisms.

We return to the original thesis: if you were going to undergo mesotherapy anyway, why do you need a genetic test? If you believe that the results of the genetic test make it more necessary for you than someone else, what is the basis for this belief? In fact, there are no such bases.

Diet recommendations

Nowadays, it is fashionable to follow a gluten-free diet. More and more companies are betting on the sale of gluten-free products, and often they are quite expensive – although, as a rule, this only implies the use of not wheat or barley, but other seeds. But not everyone who follows such a diet actually has medical indications for this.

Many confuse gluten intolerance (celiac disease) with other types of food intolerance, such as FODMAP intolerance (an acronym meaning oligosaccharides, disaccharides, monosaccharides and polyols). Celiac disease can also be caused by common IBS (irritable bowel syndrome) and SIBO (small intestine bacterial overgrowth syndrome).

Symptoms may be similar, and even triggering products may overlap, but such symptoms may have no relation to the tested genes for gluten intolerance.

There is no basis for prescribing a gluten-free diet to a person who has not been diagnosed with celiac disease by a doctor. The “gold standard” for diagnosing celiac disease is a histological study (biopsy) of the small intestine. Even serological markers (antibodies) do not have a decisive significance here.

The same goes for lactose intolerance. If a person has certain genetic variants associated with increased frequency of lactose intolerance, it does not necessarily mean that they will have it.

To determine if you are lactose intolerant, try drinking a glass of milk. If you have a clinically significant intolerance to lactose, it is hard to miss.

If you do not experience any reaction, it means that you probably do not have lactose intolerance. A more accurate test is to measure the exhaled hydrogen after consuming lactose. In any case, a genetic test is not necessary: a glass of milk is much cheaper.

If you suspect you have this condition, do not experiment in the kitchen, but see a doctor instead.

What you need to know to not be misled by pseudo-genetics

Here are the general principles that you need to know when interpreting the results of any genetic tests.

Interaction of genes and environment. Both the genotype and environmental conditions, as well as the individual development pattern, influence the features of an organism. Even twins with almost identical genomes, as you know, differ from each other.

For different traits, the relative contribution of genotype and environment is different. For example, your blood type is almost exclusively determined by your genes (changes during life are either related to blood cancer or bone marrow transplantation), while body weight is largely influenced by your diet and physical activity.

In general, having a particular variant of a gene does not necessarily mean that you have a particular feature.

Predisposition often means little. A predisposition to a certain disease or condition does not mean that this condition will necessarily occur.

Association does not mean causality. The association between mutations and certain states is primarily established through genome-wide association searches, GWAS. However, the presence of an association between a mutation and some state does not mean causality: remember false correlations, such as the correlation between chocolate consumption per capita and the number of Nobel laureates.

A risk of a fraction of a percent is not a risk. The presence of such a relationship does not say anything about the biological significance of your mutation: if the mutation statistically increases some risk, but only by a fraction of a percent, then for a scientist it may mean something, but for you personally, it means nothing.

Blood analysis is more effective than a genetic test for predisposition to a “bad” blood composition. A established genetic variant connection with a biochemical marker – the level of something in the blood, for example, inflammatory cytokines – does not mean its connection with the disease, does not mean that people with this variant feel worse and that they need to do something about it. Furthermore, this does not even mean that this marker will be elevated specifically in you: if it’s important for you to know what your IL-6 cytokine level is for some reason, go measure it, and don’t do a genetic analysis for “predisposition to its elevated level”.

A genetic test is not a basis for making a diagnosis. If you suspect that you have some illness, you need to see a good doctor and undergo a diagnosis according to the appropriate criteria, which are different for each illness. The result of a genetic test, even if it has some clinical significance, cannot under any circumstances be the only basis for making a diagnosis.

The recommendations in genetic brochures are usually unfounded. In most cases, when certain mutations (genetic variants) are detected, there is no basis for the recommendations described in the brochures. The development of recommendations given by doctors based on diagnostic results is a serious and lengthy process that involves the clinical community. Usually, such recommendations are included in clinical guidelines for the treatment and prevention of a particular illness. Among the recommendations may be not only the prescription of drugs but also diet, lifestyle changes, etc.

The existence of articles (even if there are many of them) about the connection of some mutation with an increase in the blood level of some protein cannot be the basis for the introduction of any recommendations for carriers of that mutation. The only basis can be scientific studies about the objective improvement of the condition of carriers of this mutation, who comply with such recommendations.

Genetic literacy is more valuable than genetic tests

There is also a huge stigma associated with genetic diseases and genetic risk: people associate them with concepts of “deficiency” and guilt – even if a person is simply a carrier of a pathogenic variant, and such carriers, I remind you, are almost everyone, depending on the definition of a pathogenic variant.

It is impossible not to mention the need to increase the visibility of people with genetic diseases, their destigmatization, and the development of a support system for them. It is very important to change this mentality, to tell people that being a carrier of certain genetic variants is not a stigma.

It’s sad that people for some reason don’t retain many useful knowledge and the right attitudes from biology lessons in school. I think the curriculum should be changed in such a way that people receive more practical knowledge about genetics, applicable in real life, about the methods currently used by geneticists, their limitations and significance.

In my opinion, all the information mentioned above should be taught to all school students in biology lessons. Unfortunately, this is not the case now, either the knowledge is given but the teaching method is structured in a way that students do not associate abstract concepts from the textbook with themselves and their own life and quickly forget everything.

Often people simply fear “genetics”: it is perceived as a evil rock, something that cannot be changed. But today more and more methods for treating even severe monogenic diseases are appearing.

It’s not always expensive genetic engineering drugs, there are also simple, well-known approaches: for example, one of the most common genetic diseases, phenylketonuria, can be treated with a special diet with very good results if started in time.

Thinking about genetic risks before a child is born with a pathology is significantly more constructive than searching for a “culprit” in already arisen problems. Furthermore, if both parents carry pathogenic mutations in the same gene, pre-implantation genetic testing can be performed: checking the embryos during an IVF procedure to determine which ones have inherited the pathology and which ones have not.

No one can stop people from satisfying their curiosity with their own money – it’s impossible to prevent companies from satisfying customer demand: in this sense, tests are needed to the extent that they are in demand.

However, it is important to understand that often this demand is created by the companies themselves through good marketing, telling us why we need their product.

Do not expect revelations from consumer genetic tests. Approach both the choice of test and the analysis of its results critically—if not skeptically. Serious recommendations concerning health and reproduction should definitely be verified by a geneticist doctor at a specialized clinic. Making changes in your life based on only one DTC test result can be imprudent, although if you check the information, it may turn out that there are some reasons for concern or changes.

In one of the recent studies evaluating the quality of SNP detection on microchips, based on data from the large-scale British project UK Biobank, it was found that only 16% of the time, a rare genetic variant (with a frequency less than one thousandth of a percent in the population) was correctly detected. In other cases, its detection was an error. So, before grabbing your head because of a harmful mutation detected in you, do a confirming check of the variant with Sanger sequencing: maybe you don’t actually have it.

It would be good if companies offered such services for confirming pathogenic variants detected by chips for free, but not all do. Variants detected by NGS with good coverage can be left unconfirmed if they do not fall into “problematic” regions of the genome, but it is still good to confirm if you are not sure about the quality of bioinformatics analysis. If the variant does exist, be sure to consult with a geneticist doctor regarding its real pathogenicity and what it actually means for you.

In the future, as data accumulates on the relationship between genetic variants and traits, the value of genetic testing will undoubtedly increase. It is difficult to say what impact this will have on people’s lives today. Let’s leave this to the discretion of the screenwriters, writers, and futurists.

It can only be confidently stated that scientists – medical geneticists and clinical bioinformatics – will be able to more effectively determine the genetic causes of diseases and help their patients. Knowledge is constantly accumulating, and today we know much more than even five years ago.

Often, people are simply afraid of “genetics”: it is perceived as bad luck, something they can’t change. However, there are more and more methods of treating even severe monogenic illnesses today.

It is not necessarily necessary to use expensive genetically engineered drugs. There are also simple, long-known approaches: for example, one of the most common genetic diseases, phenylketonuria, is effectively treated with a special diet if started early.

Thinking about genetic risks before a child is born with a pathology is far more productive than looking for someone to blame for problems that have already arisen. Preimplantation genetic testing can also be performed if both parents have pathogenic mutations in the same gene: checking embryos during the IVF procedure to determine which inherited the pathology and which did not.