Breakdown of human genetic variation per person, highlighting protein-coding changes and polygenic risk scores.
Image Credit: Courtesy of University of Exeter
Scientific Frontline: Extended "At a Glance" Summary: The Average Human Genome
The Core Concept: Researchers have characterized the "average" human genome using whole-genome sequencing from nearly one million individuals, revealing that extensive genetic variation, including the presence of disease-associated mutations, is a universal biological baseline rather than a physiological anomaly.
Key Distinction/Mechanism: The study establishes that the average person carries approximately five million genetic variants, including one to three rare variants definitively linked to serious genetic diseases and about fifty variants of uncertain clinical relevance, meaning the sheer presence of a high-risk gene does not inherently guarantee the development of the associated disease.
Origin/History: Led by Professor Caroline Wright at the University of Exeter, the study was published in Genome Medicine in October 2026, utilizing extensive genomic datasets from the UK Biobank and the US-based All of Us research program.
Major Frameworks/Components:
- Variant Quantification: Every genome contains roughly 10,000 variants that alter gene sequences, which can range in effect from neutral (most common) to positive or negative (e.g., lactose intolerance or varied drug responses).
- Polygenic Risk Scores: An analysis of predictive models for 28 common conditions (such as cardiovascular disease, diabetes, and schizophrenia) demonstrated that most healthy individuals rank in the high-risk category for at least three distinct conditions.
- De Novo Mutations: Individuals possess an average of 63 spontaneous mutations not present in either parent; these originate predominantly in the paternal sperm and increase at a rate of approximately 1.2 mutations for each year of the father's age.
Branch of Science: Genomics, Human Genetics, Molecular Biology, Bioinformatics
Future Application: Establishing a standardized baseline of human genetic variation will allow clinicians to accurately contextualize predictive genetic screening results, minimizing false alarms and unnecessary clinical anxiety over disease-linked variants that are biologically neutral in practice.
Why It Matters: By proving that carrying a small number of disease-associated variants is standard for the human species, this research emphasizes that genetic screening must be interpreted alongside environmental risk factors, family history, and active clinical symptoms to determine true pathological risk.
A new study has characterized the “average” human genome, providing key information on normal human genetic variation and genetic disease risk.
Researchers at the University of Exeter concluded that everyone—regardless of their current health status—could potentially be told they are at risk for numerous conditions based on their genetics alone.
Led by the University of Exeter, the study is published today in Genome Medicine and is also being presented at the American Society of Human Genetics annual meeting. The research was supported by the Medical Research Council, the Wellcome, and the NIHR Biomedical Research Center: Exeter. The team analyzed data from two major population biobanks that include whole-genome sequencing, totaling nearly one million individuals.
Key findings demonstrate that every person’s genome includes around five million variants, or locations in the DNA that differ between individuals. These include around 10,000 that alter gene sequences, which can have a positive or negative effect—ranging from lactose intolerance to drug response—but are often biologically neutral. Every person also has between one and three rare variants that have previously been shown to cause serious genetic diseases, and another 50 rare variants that are currently of uncertain clinical relevance.
The team also analyzed numerous polygenic risk scores, which take into account all known genetic factors to calculate the risk of developing a disease in the future. Looking at polygenic scores for 28 common conditions—such as diabetes, cardiovascular disease, and schizophrenia—they found that most people would be categorized as being at high genetic risk for around three conditions. The team did not investigate the health status of any of the participants, so many of these individuals might not have any diseases. The study underlines that such findings can be part of normal genetic variation, and other factors are crucial in the development of disease.
Senior author Professor Caroline Wright, at the University of Exeter, said: “Whole-genome sequencing has become such an important tool in diagnosing genetic disease, and we’re increasingly moving toward genetic screening for predicting disease. 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 world in understanding, interpreting, and contextualizing genomics.”
“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. 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 programs.”
Researchers analyzed data from the UK Biobank and the All of Us study in the US. Although the studies are large, participation is skewed toward people of Western European origin, and the research team recognizes the need for data on more diverse populations to continue to evolve understanding and impact.
Among the findings, they also discovered that individuals in the two biobanks who were recruited alongside their parents had around 63 “new” variants in their genome, not present in either parent. Known as de novo, these mutations occurred mostly in the father’s sperm and some in the mother’s eggs. The number increased particularly with the age of the father (around 1.2 more mutations per year), which has important implications for reproductive decision-making.
Published in journal: Genome Medicine
Title: The average individual genome: a survey of nearly 1 million whole-genome sequences
Authors: Harrison I. W. Wright, Robin N. Beaumont, James Fasham, Joseph S. Leslie, V. Kartik. Chundru, Timothy S. Hall, Stuart J. Cannon, Alistair T. Pagnamenta, Emma L. Baple, Andrew R. Wood, Anna Murray, Leigh Jackson, Michael N. Weedon, Kashyap Patel, Gareth Hawkes, and Caroline F. Wright
Source/Credit: University of Exeter | Louise Vennells
Edited by: Scientific Frontline
Reference Number: geno102226_01
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