DNA is not a verdict

Genetic tests – what are they really talking about?

The publishing house "Mann, Ivanov and Ferber" publishes the book "DNA is not a sentence." TASS publishes an excerpt on how to understand the results of genetic tests and news about the genes of thinness, depression, crime.

For centuries, it was believed that human nature was determined by God (many still believe this). Genetics gave an alternative explanation. It would seem that religious and scientific concepts have nothing in common, but in fact their perception is similar: genes cause the same sacred awe as the revelations of the prophets once did.

Sensational notes keep appearing in the media that the roots of diseases, character, and addictions are found in the sequences of molecules from our cells. Sometimes it's true and one "typo" in the DNA is enough to turn life upside down. But much more often, genes "work" not so straightforwardly, and scientists are not completely sure about this. If it is still unknown how many genes a person has (and what is generally understood by this word), then what to say about their functions.

News is still okay, but different companies, including in Russia, offer to undergo genetic tests for a tidy sum. How to understand the results of such tests and what geneticists can judge today – in an excerpt from the book by psychologist Stephen Heine "DNA is not a verdict. An amazing connection between you and your genes."

First of all, it is necessary to remember that the effects of genes can be different. It is necessary to pay special attention to the degree of influence. When it comes to the effects of genetic factors, size matters. Many genes cause the development of rare conditions, such as Huntington's disease, FOP (fibrodysplasia, when soft tissues turn into bones – approx. TASS), or cystic fibrosis. When these genes are detected, it is possible to predict a particular disease with almost 100% accuracy. In addition, the influence of a number of genes is somewhat lower, but still significant. For example, these include BRCA1, the carrier of which is Angelina Jolie. In the presence of this gene, the risk of developing breast cancer ranges from 40 to 60%. With such a high degree of risk, the idea of genes as switches is close to reality.

Nevertheless, we often use this logic and consider certain genes to be markers of diseases even in cases of weak genetic influences, when the contribution of individual genes is minimal. This is the majority of our personal qualities and states. They are the result of the combined influence of many different genes, which in turn are influenced by experience and epigenetic processes. The idea of genes as switches leads to absolutely incorrect conclusions and unfounded fears much more often than it correctly reflects reality.

Since you have focused your attention on the scale of genetic influences, then it would be logical to match the strength of the emotional reaction and the weight of a certain genetic factor. Finding a balance between the emotional response and the existing genetic risk is not an easy task. This is difficult for two reasons. Firstly, thinking in terms of probability is not an innate and natural property of a person. Secondly, we often consider internal, essential risk factors to be unavoidable by nature, regardless of their strength. No matter how insignificant the "increased" risk of Parkinson's disease is, when I think that genes make me more vulnerable to this disease or – even worse – that I am a carrier of the "Parkinson's gene", I am horrified. It seems that my essence itself is plotting against my health and well-being.

Another difficulty in assessing risks is the fact that we subjectively tend to consider serious problems more likely than small ones, even if the actual risks are the same. For example, if there is a 20% chance that it will rain in your area tomorrow, then you will decide that, most likely, it will not. At the same time, if a tornado is expected in your area with a 20% probability tomorrow, then you will be wary and consider the risk more than possible. The danger of a tornado makes us believe more in the forecast, although in fact it is as likely as rain. Dangerous situations and conditions, fortunately, are rare. Therefore, any probability of their occurrence exceeding zero (such as, for example, the 2.1% risk of my developing Parkinson's disease) may seem much more significant than its actual value. The discrepancy between the subjective assessment and the real possibility forces genetic consultants, in particular, to oppose the fact that clients are given accurate estimates of their genetic risks. In fact, people often cannot remember their indicators regarding the likelihood of developing a particular condition, even immediately after consulting on the results of genome decoding. One of the founders of genetic counseling – Sheldon Reed – claims that many clients "often do not make any distinction between one chance in four and one chance in a hundred. It's the same thing for them." Some perceive both of these probabilities as follows: "This could happen to me."

The disparity between subjective concern and actual probabilities is also found by many genetic consultants. They often view any level of risk above 0% as noteworthy. According to the survey, the probability of 2% of having a child with a genetic disease was estimated by about half of the genetics consultants as "high" or even "very high". At the same time, many said that "there is no acceptable risk." Regardless of whether we treat consultants or their clients, our fears do not allow us to objectively assess the actual possibility of a particular outcome.

Together with Benjamin Cheng, we investigated how much immunity to the magnitude of genetic risk will affect people's reaction to other genetic factors, in particular the hypothesis of the so-called crime genes. Adult Americans were given a note to read about the case when college student Patrick killed another person with a knife during a fight. One group of participants in the experiment learned that Patrick was a carrier of a gene that increased the likelihood of violence by 25%. Others read exactly the same brief description of the incident, but with one exception: the gene increased the possibility of violent actions by 400%. The note that the third group read did not mention Patrick's genes. Then all participants were asked to decide whether the defense based on insanity would allow the student's sentence to be commuted. The first two groups considered this line of defense more suitable than the third. But the degree of genetic dependence had almost no effect on their opinion. The respondents answered the same regardless of whether the genetic predisposition to violence was only 25% or all 400%. It seemed to matter to these participants that Patrick had a genetic risk (of any degree), which made him not fully responsible for his crime in their eyes. When we hear about the connection of something with genes, we automatically come to the conclusion that "it is genetically determined." When it comes to the actual amount of genetic influence, we ignore this information. And we react to any such information as a message that the genes have worked as switches.

Unreasonable reactions to information about genes raise even more questions in light of the unpleasant fact that genetic research itself is far from being so accurate. Many genetic discoveries (if not most of them), information about which is published in leading journals and then replicated in newspapers around the world, turn out to be fake. In one article, "The American Journal of Medical Genetics. Part B" says: "It's no secret that thousands of studies of candidate gene associations have been published in our field. But with reproducible results – quite a bit." Genome-wide association search is experiencing similar problems. Most often, due to pure chance, imaginary gene associations are revealed. Even if the associations found are reliable, they are usually too insignificant to have any significant impact on our lives. Journalist David Dobbs describes our attitudes towards genetic research as developing in an arc. At the same time, the discoveries serve as "a source of tempting hope, festive hype and bitter disappointment." Unfortunately, given the tendency of scientific journals and newspapers to admire breakthroughs in a particular field, we all hear about amazing discoveries. But often we never know about subsequent unsuccessful attempts to reproduce the results obtained. Scientists' conclusions are also not reported if they eventually realize that reality is not nearly as interesting as the original discovery. For example, in 2009, during a genome–wide association search, a special type of ONP was found at the rs4307059 locus (that is, there is only one "letter" difference in this DNA location - approx. TASS), which was identified as a risk factor for autism. It was claimed that the probability of its accidental detection is less than 0.00001%, which implies a high reliability of this marker. The New York Daily News published an article about this study, which noted that the newly discovered gene increases the risk of developing autism by 20%. The following scientific work, published in the same year, allowed us to conclude that the probability of developing autism in people with the same genetic marker is actually lower than average. But this unsuccessful attempt to reproduce the results of the study was not covered in the media. Such failures are very common. Consequently, we not only exaggerate the significance of weak genetic influences that actually exist, but also worry about discoveries that did not take place at all. These ghostly fears are akin to the fear that zombies will attack you while you sleep.

Why do the results of genetic research so often fail the test of time? There are two answers to this question. Firstly, there is the same problem in the field of genetics as in other scientific fields. Scientists are rewarded for their publications. And this leads to many "discoveries" that are covered in scientific journals and other media even before receiving confirmation that these data are reliable. The difference between discovering something new and proving that it is indeed a discovery, the results of which can be reproduced with a high degree of accuracy by other researchers, is huge.

The second reason why the results of many genetic studies are not reproducible is rather related to the specifics of this area. The fact is that, fortunately, most of the phenotypes are formed under the weak influence of individual genes. Therefore, the vast majority of genetic associations are very insignificant, and it is almost impossible to reliably observe them. They are like a faint whisper amid the loud noise of all the other factors that influence our lives. And when scientists think that they have heard this small voice, in fact, they often find themselves at the mercy of illusions.

Consider the so-called novelty-seeking gene, which is a certain variation of the DRD4 gene. This is one of the most well-studied genes in behavioral genetics. He aroused great interest in the media, which also gave him several other names, such as "the gene of liberalism" or "the gene of risk". In 2015, Land Rover used this gene in an advertising campaign for its Discovery Sport car. It has been dubbed the "adventurism gene." The brand's developers explicitly stated that "if you are a carrier of this gene, then you are more inclined to adventure and risk." Given the huge amount of research on this topic and the media interest in this gene, it would seem very important to know which allele you are the owner of. But to what extent does this well-studied gene actually determine the craving for novelty, adventure and risk? The degree of its influence is approximately 0.1%! And even this figure, apparently, is exaggerated. Attempts to establish someone's tendency to search for novelty, relying only on information about the presence of this gene, are like trying to imagine the whole mosaic on just one fragment out of 1000.

Every time you hear about a single genetic variation that can determine a certain property or condition, it's worth focusing on assessing its strength. If a certain gene has a great influence on the presence of a certain trait or the risk of developing a certain condition (which is rare), then you really should pay attention to it. Especially if you are a carrier of this variation. Most likely, this variation will portend the development of some rare genetic disease, so you should seek medical advice. But most of the genetic predictions provided by biotech companies to consumers are based on such weak associations and are so inaccurate that they should simply be ignored. An even better solution would be to save money and not apply for such risk assessments at all. Fragmentary and unsubstantiated information about genetic influences will lead to nothing but anxiety, even if the very impact of a particular gene on your life is not in sight.

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