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Scientists discovered that aging DNA repeats expand at wildly different speeds—and in some people, the consequences can be devastating.
A sweeping genetic study drawing on data from more than 900,000 people reveals that some parts of human DNA become increasingly unstable over time. These regions consist of very short genetic sequences that repeat again and again, and the research shows that they tend to lengthen as people get older.
The analysis also found that common inherited genetic differences can dramatically influence how fast this expansion happens, with some people experiencing changes up to four times faster than others. In certain cases, expanded DNA repeats were strongly linked to serious health problems, including kidney failure and liver disease.
Why Expanding DNA Repeats Matter for Health
Expanded DNA repeats are already known to cause more than 60 inherited disorders. These conditions arise when repetitive genetic sequences grow beyond a safe length and disrupt normal cell function. Well known examples include Huntington’s disease, myotonic dystrophy, and some forms of ALS.
While most people carry DNA repeats that slowly expand throughout life, scientists had not fully examined how widespread this instability is or which genes influence it using large-scale population data. This new research shows that repeat expansion is far more common than previously understood. It also pinpoints dozens of genes involved in controlling the process, offering promising new directions for treatments designed to slow disease progression.
How Researchers Analyzed Nearly a Million Genomes
Scientists from UCLA, the Broad Institute, and Harvard Medical School examined whole genome sequencing data from 490,416 participants in the UK Biobank and 414,830 participants in the All of Us Research Program. To do this, they created new computational tools capable of detecting and measuring DNA repeat length and instability using standard sequencing data.
The team analyzed 356,131 variable repeat sites across the genome. They tracked how these repeats changed with age in blood cells and identified inherited genetic variants that affected how quickly the repeats expanded. The researchers also searched for connections between repeat expansion and thousands of disease outcomes in order to uncover previously unknown links to human illness.
Key Discoveries From the Study
The analysis showed that common DNA repeats in blood cells consistently expand as people age. Researchers identified 29 regions of the genome where inherited genetic variants altered the speed of repeat expansion. The difference between individuals with the highest and lowest genetic risk scores reached as much as a fourfold change.
One unexpected finding was that the same DNA repair genes did not act uniformly. Genetic variants that stabilized certain repeats caused instability in others. This suggests that DNA repair processes can behave very differently depending on the genetic context.
The study also uncovered a previously unrecognized repeat expansion disorder. Expansions in the GLS gene, which occur in about 0.03% of people, were linked to a 14-fold increase in the risk of severe kidney disease and a 3-fold increase in liver disease risk.
What These Findings Mean Going Forward
The results suggest that measuring DNA repeat expansion in blood could serve as a useful biomarker for evaluating future treatments aimed at slowing repeat growth in conditions such as Huntington’s disease. The computational methods developed for this work can now be applied to other large biobank datasets to identify additional unstable repeats and disease associations.
Researchers note that more detailed laboratory studies will be needed to explain why the same genetic modifiers can have opposite effects on different DNA repeats. Understanding how DNA repair pathways operate across various cell types and genetic backgrounds will be key. The newly identified GLS related kidney and liver disease also raises the possibility that other repeat expansion disorders remain hidden in existing genetic data.
Expert Perspective
“We found that most human genomes contain repeat elements that expand as we age,” said Margaux L. A. Hujoel, PhD, lead author of the study and assistant professor in the Departments of Human Genetics and Computational Medicine at the David Geffen School of Medicine at UCLA.
“The strong genetic control of this expansion, with some individuals’ repeats expanding four times faster than others, points to opportunities for therapeutic intervention. These naturally occurring genetic modifiers show us which molecular pathways could be targeted to slow repeat expansion in disease.”
Reference: “Insights into DNA repeat expansions among 900,000 biobank participants” 7 January 2026, Nature.
DOI: 10.1038/s41586-025-09886-z
About the Research Team
Margaux L. A. Hujoel (UCLA and Brigham and Women’s Hospital/Harvard Medical School), Robert E. Handsaker (Broad Institute and Harvard Medical School), David Tang (Brigham and Women’s Hospital/Harvard Medical School), Nolan Kamitaki (Brigham and Women’s Hospital/Harvard Medical School), Ronen E. Mukamel (Brigham and Women’s Hospital/Harvard Medical School), Simone Rubinacci (Brigham and Women’s Hospital/Harvard Medical School and Institute for Molecular Medicine Finland), Pier Francesco Palamara (University of Oxford), Steven A. McCarroll (Broad Institute and Harvard Medical School), Po-Ru Loh (Brigham and Women’s Hospital/Harvard Medical School and Broad Institute)
Funding and Disclosures
M.L.A.H. was supported by US NIH fellowship F32 HL160061; R.E.H. and S.A.M. by US NIH grant R01 HG006855; D.T. by US NIH training grant T32 HG002295; N.K. by US NIH training grant T32 HG002295 and fellowship F31 DE034283; R.E.M. by US NIH grant K25 HL150334; S.R. by a Swiss National Science Foundation Postdoc. Mobility fellowship; P.F.P. by ERC Starting Grant no. 850869; and P.-R.L. by US NIH grants R56 HG012698, R01 HG013110 and UM1 DA058230 and a Burroughs Wellcome Fund Career Award. The All of Us Research Program is supported by the NIH. The authors declare no competing interests.
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