Genetic testing

What is behind it

Most offerings work with a genotyping chip. It checks hundreds of thousands of known single-base variants, so-called SNPs, at fixed positions in the genome. This is inexpensive and reliable for common variants. A chip, however, captures rare, disease-relevant changes poorly. That requires targeted sequencing in a clinical laboratory.

The variants give rise to three kinds of statements. First, monogenic findings: a variant in one gene explains a high risk, for example of certain hereditary forms of cancer. Second, pharmacogenetic findings: variants in enzyme genes change how quickly you break down a medicine. Third, polygenic risk scores and lifestyle profiles that bundle many small effects into one number, for example for heart risk, caffeine tolerance or the supposedly suitable type of training.

Where genetic tests really change something

Pharmacogenetics is the part that reaches everyday practice. The enzyme CYP2D6 converts tramadol and codeine, among others. According to the Association of Statutory Health Insurance Physicians of Baden-Württemberg, it is functionally absent in about 10 percent of people in Europe and works at a reduced level in about 30 percent. The painkiller then works less well than expected.

The case of chemotherapy with 5-fluorouracil and related agents is even clearer. The enzyme DPD breaks them down. Since 2020, BfArM and EMA have recommended testing for DPD deficiency before starting treatment, because those affected can develop severe, sometimes life-threatening side effects. An estimated 3 to 9 percent of the population of European descent have a partial deficiency. The genetic test for it has been covered by statutory health insurance since October 1, 2020.

What it costs and who pays

Statutory health insurance covers genetic diagnostics when there is a medical question: a suspected hereditary disease, a conspicuous family history, certain medicines. Many pharmacogenetic tests, however, are not yet in the benefits catalogue; reimbursement is then possible only in individual cases. Panels on nutrition, sport, skin ageing or general health risk are self-pay services.

How to recognize a reputable offering

In Germany, the Genetic Diagnostics Act (Gendiagnostikgesetz) regulates medical tests. A diagnostic test may only be ordered by a physician; a predictive one, that is, a prediction of future diseases, only by a specialist in human genetics or a suitably qualified physician. Genetic counselling is mandatory before and after a predictive test. An offering that delivers disease risks by post without medical information and counselling does not meet this framework.

Further points to check: Is it stated clearly which genes and variants are examined and with which method? Are abnormal findings confirmed in a clinical laboratory? Where are your data stored, and can you have them deleted? And for nutrition and sport recommendations, is it stated openly that the benefit is not proven?

What the studies show

PREPARE: medicines guided by a gene panel

Open-label, cluster-randomized crossover trial at hospitals, health centres and pharmacies in seven countries, 6,944 adults with a first prescription. 50 variants in 12 genes were tested, and therapy was adjusted according to the recommendations of a Dutch expert group. The primary endpoint, clinically relevant adverse effects within 12 weeks, was met: 21.5 versus 28.6 percent. Weakness: no blinding.

DIETFITS: which diet suits my genes

Randomized trial with 609 adults with overweight, 12 months of a healthy low-fat or a healthy low-carbohydrate diet. Both groups lost a similar amount of weight, 5.3 and 6.0 kilograms. A gene pattern of three variants that was supposed to predict the suitable diet had no influence on success.

Food4Me: counselling with and without genes

Internet-based randomized trial in seven European countries; 1,269 participants completed it. After 6 months, personalized counselling improved diet compared with standard advice. When blood values and 5 nutrition-relevant gene variants were added, the counselling did not become more effective.

Hollands 2016: does a genetic risk change behaviour

Meta-analysis of 18 controlled studies. People who learned their DNA-based disease risk did not smoke less, did not exercise more and did not eat significantly differently. Anxiety or depression did not increase either. Study quality was mostly low.

Where the data stop

Polygenic risk scores sound precise but discriminate poorly for the individual. According to an analysis by the epidemiologist Aroon Hingorani, a typical score for a common disease detects 11 percent of later cases if 5 percent false alarms are allowed. That is useful for population research, but of little use as a personal health check.

A second problem is the measurement quality of consumer chips for rare variants. A clinical laboratory re-checked 49 samples in which raw data from a consumer test had reported a disease-relevant variant. 40 percent of them were false positives. The sample was small and selected; the direction is nevertheless clear. For sports genetics, that is, training plans based on a gene profile, no controlled study with a clinical endpoint was found.

Status, approval and legal

Medical genetic tests fall under the German Genetic Diagnostics Act: physician reservation, for predictive tests specialist reservation and mandatory counselling. Tests on the effect of medicines count as diagnostic. Statutory health insurance pays when there is a medical indication; individual pharmacogenetic tests such as DPD testing are in the benefits catalogue, many others are not. Insurers may neither require a genetic test nor use existing results. Exception: for life, occupational disability and long-term care annuity insurance with benefits above 300,000 euros or an annual annuity above 30,000 euros, known results must be disclosed.

Safety

Physically, a genetic analysis is harmless; a saliva sample is usually enough. The risks lie elsewhere: incorrect findings, false reassurance from an unremarkable profile, unnecessary worry from an abnormal one, and permanently sensitive data that also concern your relatives. Take a pharmacogenetic result to your physician instead of changing medicines yourself, because dose and choice of active substance depend on more than one gene.

Sources

• Swen JJ et al., Lancet 2023 (PREPARE)
• Gardner CD et al., JAMA 2018 (DIETFITS)
• Celis-Morales C et al., Int J Epidemiol 2017 (Food4Me)
• Hollands GJ et al., BMJ 2016
• Hingorani AD, J Med Screen 2025
• Tandy-Connor S et al., Genet Med 2018
• BfArM, Dear Healthcare Professional Letter (Rote-Hand-Brief) on fluoropyrimidines, 2020
• KV Baden-Württemberg, Verordnungsforum 61, 2022
• German Genetic Diagnostics Act (Gendiagnostikgesetz) § 7, physician reservation
• German Genetic Diagnostics Act (Gendiagnostikgesetz) § 18, insurance