Most of us carry genetic risks. Does that mean we'll get sick?

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Most people would be classified as having a high genetic risk for around three common diseases, including diabetes, cardiovascular disease and schizophrenia. But most of us are not destined to become ill, according to a new study. It is that genetic risk is far more common than the disease itself -- and the two should not be confused.

Published in the journal Genome Medicine on October 22, the study set out to describe what a typical human genome looks like and how much genetic variation people carry, including variations associated with disease. Researchers led by the University of Exeter analysed genetic data from nearly one million people in the UK Biobank and the US All of Us research programme. Their findings offer a useful lesson in how to interpret genetic tests, and why a concerning result on a DNA report is not necessarily a prediction of what will happen to your health.

The study is significant because it offers a useful corrective to the idea that our DNA can neatly predict our medical future. Our genomes contain millions of differences, and many people carry genetic variants associated with disease. Yet the presence of these variants does not translate directly into illness.

The key findings

1. Most people have a high genetic score for around three common conditions: The researchers examined genetic risk scores for 28 diseases in the UK Biobank dataset. On average, participants fell within the top 10% of genetic risk scores for around three conditions. These scores combine information from many genetic variants, each of which may contribute a small amount to a person's predisposition to a disease.

Being in the top 10% means having a higher score than most people in the comparison group. It does not mean having a 10% chance of developing the disease, nor does it mean that the disease is inevitable.

The study also did not establish that the people with higher scores would go on to develop those conditions.

2. Everyone's DNA contains enormous amounts of variation: The average genome contains roughly 4.3 million to 5.3 million genetic variants -- differences in DNA compared with a reference genome. Most are harmless or have no clearly measurable effect on health. Some influence ordinary traits like how the body processes substances or how a person responds to medicines. A much smaller number has established links to disease.

In other words, genetic variation is normal. Finding a difference in someone's DNA is not, by itself, evidence that something is wrong.

3. A disease-associated genetic variant does not always cause disease: Researchers estimated that an average person carries around one to three rare variants classified as pathogenic or likely pathogenic in certain genes associated with single-gene disorders. That may sound alarming, but many of these variants occur in genes linked to recessive conditions. A person who carries just one disease-causing copy may be a healthy carrier rather than someone who has the disease.

4. Genetic testing can produce uncertain results: The study also found that people carry numerous rare genetic variants whose clinical significance is not yet known -- around 50 variants of uncertain significance on average under the study's definitions.

An uncertain result is not a diagnosis. It means researchers do not yet have enough evidence to determine whether the variant affects health.

As genetic databases grow and scientific understanding improves, some interpretations may change. This is one reason why genetic reports need careful clinical interpretation rather than being read as a list of diseases a person is likely to get.

What does "high genetic risk" actually mean?

Imagine two people with similar lifestyles. One has a genetic profile that places them above average for type 2 diabetes risk, while the other has a lower score. The first person may have a greater inherited predisposition. But whether either person develops diabetes also depends on other influences, including age, body composition, physical activity, diet, medical history and other biological factors. Genes are part of the picture, not the whole picture.

The study's results are, therefore, best understood as a warning against treating genetic scores as stand-alone forecasts.

Does this mean genetic testing is not useful?

No. Genetic testing can be extremely valuable when used for the right purpose. It can help diagnose certain inherited disorders, identify people who may benefit from specific preventive measures, guide some treatment decisions and clarify the risk of particular conditions within families.

But the usefulness of a test depends on what it measures and how reliably its findings predict a meaningful health outcome. A test designed to help diagnose an inherited disorder is not the same as a broad screening test that calculates scores for dozens of common diseases. The latter may flag many people without reliably identifying who will actually become ill. The researchers caution that reporting numerous genetic risk scores together could lead to unnecessary anxiety, follow-up testing and overdiagnosis.

What about people in India and other under-represented populations?

Although the research involved nearly one million people, the data came from the UK and the US, and people of Western European ancestry were over-represented. The researchers acknowledge the need for more diverse genetic datasets. More representative research will be needed to establish how well these risk scores work across different populations.