Researchers led by the UK's University of Exeter described the characteristics of the “average” human genome, finding that everyone, regardless of their current health status, could be considered genetically at risk for numerous conditions.
The findings, published in the journal Genome Medicine, reveal that every person's genome contains around five million variants, or DNA locations that differ between individuals.
Among these are around 10,000 variants that alter gene sequences and can have positive or negative effects. Their potential effects range from lactose intolerance to responses to drugs, although many variants are biologically neutral, the researchers found.
Each person also carries between one and three rare variants previously shown to cause serious genetic diseases, along with another 50 rare variants whose clinical relevance remains uncertain.
The research team analysed data from two major population biobanks, the UK Biobank and the US' All of Us, which include whole genome sequencing data covering nearly one million individuals.
Senior author Caroline Wright, from the University of Exeter, said whole genome sequencing had become an important tool for diagnosing genetic diseases, with genetic screening increasingly being used to predict disease risks.
“Yet most people are unaware of just how much genetic variation is present in every genome. Actually, variation is the norm. For the first time, our study outlines what to expect in the average human genome, which can benefit clinicians and patients across the word in understanding, interpreting and contextualising genomics,” Wright said.
The researchers also examined numerous polygenic risk scores, which combine all known genetic factors to calculate a person's future risk of developing a disease.
Applying polygenic scores (PGS) for 28 common diseases within the UK Biobank (UKB), the researchers estimated that the average person falls within the top 10 per cent for nearly three conditions. They also found that around one in five people falls within the top one per cent for at least one polygenic risk score.
“Importantly, we found that everyone carries a small number of genetic variants linked to disease, although many of these will not actually cause disease in that individual,” Wright said.
The senior author stressed that genetic findings must be interpreted in context, taking into account symptoms, family history, and other clinical and environmental risk factors.
“It is therefore crucial to consider context when interpreting findings from genetic testing, including symptoms or family history of disease as well as other clinical and environmental risk factors. Our findings also provide important context for professionals who are interpreting genetic testing results or commissioning genetic screening programmes,” Wright added.
Despite the scale of the datasets, the researchers acknowledged an important limitation: participation was skewed towards people of Western European origin. They said data from more diverse populations would be needed to improve understanding and strengthen the impact of the findings.
The study underscores the distinction between carrying genetic variants associated with disease and actually developing a condition, highlighting the importance of clinical context when interpreting genetic risks and using genetic screening to assess future health outcomes.
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