Genetic testing for preventive health care

The medical application of genetic analysis

Learn how gene analyses find their clinical application and what the advantages are.

The future of medicine, in which everyone will have their entire genome sequenced to infer better person-specific preventive measures, is impatiently awaited by many medical professionals. Where are we in science and what is possible now?

That the approximately 30,000 human genes play a role in health is undisputed. Currently, there are already 800 different medical gene analyses available from Novogenia. Worldwide, there are even more than 2,000 [1]. Among them are many diagnostic tests for monogenic diseases, some of which are very rare, but the genetic component of common widespread diseases is also becoming increasingly clear.

Genetic analyses have various applications in practice. On the one hand, they are used to confirm a suspected diagnosis (as in the case of cystic fibrosis – CFTR gene [6]) or to assess the risk of first-degree relatives (breast cancer – BRCA1 & BRCA2 gene [7]).
While some genetic findings represent an absolute fate for the patient’s health, others merely increase the individual’s risk of developing the disease. Since the development of many diseases depends on an interplay between genes and environment/lifestyle, this opens up novel opportunities in prevention as well.

“If we know about our genetic predisposition to certain diseases even before the first symptoms, we can adjust our environment, our lifestyle, to avoid certain risk factors and potentially prevent the development of the disease,”

says Dr. Daniel Wallerstorfer, CEO of Novogenia. Well-researched examples now abound.

For example, familial hemochromatosis or iron storage disease is mainly caused by defects in the HFE gene [8]. Men carrying defects in both genes of this type suffer from iron overload (elevated transferrin saturation and serum ferritin) in 75 to 96% and up to 50% from other symptoms up to clinically manifest hemochromatosis [3, 4]. Despite its frequency, the disease is misdiagnosed and not properly treated in 67% of cases [5], which can lead to a number of sequelae such as joint disease, susceptibility to infection, diabetes mellitus, and hepatic cerebrovascular disease [9-12].

Currently, genetic analyses are mainly used to confirm a diagnosis and to assess the risk of close relatives, although there is great potential in the prevention of asymptomatic mutation carriers, especially in this disease. Just as in the usual treatment of hemochromatosis (phlebotomy therapy), in the presymptomatic stage, regular blood donation can lower the iron level in the body and keep it within the normal range. The development of secondary diseases is virtually excluded with such precautions and medical monitoring [13, 14].

“So there is a clear benefit for people affected by these genetic defects to know about their risk,” Dr. Wallerstorfer said. “Unfortunately, to this day, very few people know about their risk.”

Genetic test instead of anamnesis?

Although a medical history can achieve a similar informative value as a genetic analysis in genetic diseases with high penetrance and dominant inheritance, it very quickly reaches its limits in most cases.

For example, in the case of Huntington’s disease, a dominant gene defect leading to disease in any individual (so-called complete penetrance) is easily traced by history through the family tree [15]. If a carrier of this genetic defect has a child, he or she will pass on 50% of the predisposition. A medical history can only make guesses here and estimate the probability of disease at 50%. Only a genetic analysis can provide absolute clarity here and determine whether the genetic defect has been passed on and whether the disease will occur.

In diseases with incomplete penetrance (not every carrier of the mutation develops the disease), such as familial thrombophilia, it becomes even more difficult to work with medical histories. These genetic defects are relatively common and are found in approximately 20-40% of thrombosis cases. About one in twenty Europeans is genetically predisposed to thrombophilia and at 8 times the risk of thrombosis [16-18]. This means that untreated, affected individuals will develop a potentially fatal thrombosis in about 10% of cases in their lifetime [19]. Since these genetic defects do not lead to disease in every individual and only 50% of each is passed on to the next generation, they are difficult to track or even detect by history.

Diseases such as hemochromatosis or lactose intolerance are inherited recessively, meaning that a person must have inherited a genetic defect from each parent for the disease to occur. Carriers of only one genetic defect do not develop symptoms and, without genetic analysis, do not know that they are carriers of the predisposition. Therefore, in these cases, a medical history is useless, since the cases of the disease occur sporadically, without family members being affected.

Examples from practice

The significance of gene analyses often varies from disease pattern to disease pattern, from gene to gene, and even from mutation to mutation. In addition, such genetic analyses provide different information and opportunities for prevention. Here are some examples of already well-researched genetic predispositions and prevention options.

Lactose intolerance

The presence of two genetic defects affecting the LCT gene predicts with very high probability (>90%) the development of lactose intolerance during life [20-22]. However, the age at which intolerance develops the first symptoms is highly variable and depends on the general health of the person. While a lactose tolerance test (hydrogen test or hydrogen breath test) provides a snapshot of health status, it cannot predict the patient’s future health. A positive genetic analysis result, on the other hand, can predict intolerance in the future with a very high probability. Reducing lactose in the diet and paying attention to symptoms can spare sufferers the usual years of digestive discomfort of unexplained cause.

Familial thrombophilia

A single genetic defect (Factor V Leiden) increases the risk of thrombosis 8-fold and leads to thrombosis in 10% of affected individuals during their lifetime. If two genetic defects are present, the risk increases about 80-fold and, if left untreated, almost invariably leads to the development of the disease in the course of life. According to studies, such genetic defects are involved in about 40% of thrombosis cases [6-19]. For prophylaxis, lifestyle changes and drug therapies (especially in risk situations such as long flights or after surgery) are available that can normalize this genetic predisposition.

For women, these genetic dispositions pose a particular risk. The use of hormonal contraception or hormonal preparations doubles the individual risk of thrombosis even without a genetic defect. If a mostly unknown predisposition to thrombophilia is then added, the risk of disease increases exponentially to 18-fold [23, 24]. Therefore, it is also generally accepted that women with a genetic disposition should switch to alternative non-hormonal contraceptives. The only problem is that hardly any affected woman knows that this risk lies dormant in her genes. It becomes even more serious for women during pregnancy. The already 4-fold increased risk of thrombosis increases to 60-fold due to a genetic defect, a condition that should definitely be treated with low-molecular-weight heparin [25, 26].

Familial hypercholesterolemia

A gene defect in the APOB gene increases the likelihood of hypercholesterolemia by 78-fold, and some defects in the LDLR gene increase it by as much as 1233-fold [27-29]. These forms of hypercholesterolemia are often indistinguishable from acquired cholesterolemias, but may require different treatment and monitoring.


About one in three women carries a genetic defect that increases their risk of osteoporosis by 26%. One in 33 women carries two genetic defects that together increase the risk by 178% [30]. Preserving bone mass is much easier than rebuilding lost bone mass, so identifying genetically predisposed individuals as early as possible is important to intervene early in the course of the disease. If the risk is detected early, the corresponding bone parts can be strengthened at a young age and the degradation of the bones can be slowed down by a diet that is particularly rich in calcium and vitamin D and low in phosphate [31-34].

Gluten intolerance / Celiac disease

This autoimmune disease is triggered, among other things, by certain HLA types, which are necessary for a disease but not yet predictive. Thus, a negative finding for the risk HLA types rules out the possibility of celiac disease with a very high probability. Because this disease is misdiagnosed for an average of 11 years and is estimated to have fatal consequences in 12% of untreated cases, identification of those at risk is particularly important [35-37]. If symptoms subsequently occur, they can be quickly assigned and confirmed by further laboratory chemistry tests. Health risks such as lactose intolerance, a 9-fold ENT tumor risk, and up to an 80-fold lymphoma risk are restored to normal with adequate treatment and a gluten-free diet [35-37].


Macular Degeneration

A common genetic defect in the CFH gene increases the risk of developing macular degeneration by 4 to 12 times, depending on the number of genetic defects. Classification into risk groups (1-fold/4-fold/12-fold) allows better determination of individual risk [38, 39]. High-risk patients are recommended a diet especially rich in antioxidants, the use of UV-protective sunglasses, the use of a home test to detect visual field distortion, and regular medical checkups [40-45].

Nutritional Genomics

Fruit is healthy and fatty meat is unhealthy. Such nutritional principles are common knowledge and a conscious diet is also advisable to everyone. However, these rules were put together with the idea that they should apply to the general public. However, individual predispositions are not taken into account.

For example, dairy products are a recommended source of calcium. A diet above average in calcium plays an essential role, especially for people who are genetically predisposed to bone loss (osteoporosis). So dairy products are highly recommended unless that person is one of the 20% of the population that cannot tolerate lactose (milk sugar) due to an inherited genetic defect [21]. In this case, lactose-containing dairy products should be avoided altogether and a switch made to other sources of calcium such as broccoli or dietary supplements. Genetic predispositions to elevated cholesterol or triglycerides (arteriosclerosis), diabetes mellitus type 2 (diabetes), gluten intolerance (celiac disease), iron storage disease (hemochromatosis) or macular degeneration also require specific changes in diet in order to take optimal precautions against these diseases. Genetic analyses can be used to classify certain food categories as particularly important or not recommended in order to counteract genetic predispositions as best as possible.

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