Our genes play a surprisingly large role in how quickly our DNA changes as we age, according to a new study. while lifestyle choices certainly matter, research from two large biobanks reveals that genetic factors significantly influence the rate of DNA mutation.
Genetic blueprint of Aging: It’s More Complex Than We Thought
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New research identifies dozens of genes that control the expansion of DNA repeats, offering potential targets for slowing genetic disease progression.
- Researchers analyzed data from nearly 910,000 participants in the UK Biobank and the All of Us Research Program.
- The study pinpointed 29 genetic locations that influence the expansion of DNA repeats in blood cells.
- these findings could lead to blood-based biomarkers for tracking the effectiveness of therapies for diseases like Huntington’s.
- A newly identified DNA repeat expansion in the GLS gene is linked to increased risk of kidney and liver disease.
The study, published in Nature, revealed dozens of genes that regulate the expansion of DNA repeats-short genetic sequences that become longer and more unstable with age. These expanded repeats are surprisingly common, present in the genomes of most people and far more widespread than previously understood.
DNA Repeats and Inherited Diseases
Expanded DNA repeats are responsible for over 60 inherited diseases, including Huntington’s disease and myotonic dystrophy. researchers from the University of California at Los Angeles and other institutions studied whole-genome sequencing (WGS) data from 490,416 participants in the UK Biobank and 414,830 participants from the All of Us Research Program, an initiative from the U.S. National Institutes of Health.
The team meticulously measured DNA repeat length and instability, examining 356,131 polymorphic repeat locations across the entire genome. Results showed that common DNA repeats in blood cells grow in length as a person ages, and that most human genomes contain repeat elements that expand with aging. Repeats at different locations showed widely varying tendencies to mutate in blood and germline cells.
“The strong genetic control of this expansion, with some individuals’ repeats expanding four times faster than others, points to opportunities for therapeutic intervention,” explained researcher Margaux Hujoel, phd. “These naturally occurring genetic modifiers show us which molecular pathways could be targeted to slow repeat expansion in disease.”
New Biomarker Potential
The researchers identified 29 specific genetic locations where inherited variants increased the expansion of DNA repeats in blood. These variants had varying impacts and collectively influenced repeat instability. At one repeat location, expansion rates differed fourfold between individuals with the highest and lowest polygenic risk scores.
Interestingly, the same DNA repair genes could have opposing effects on different DNA repeats, stabilizing some while destabilizing others.The study also identified a new repeat expansion disorder involving the GLS gene, found in approximately 0.03% of people. This expansion was associated with a 14-fold increased risk of severe kidney disease and a tripled risk of liver diseases.
The researchers suggest that measuring unstable DNA repeats in blood could one day serve as biomarkers to assess the effectiveness of treatments designed to slow the progression of genetic diseases. “The analytical tools that we have developed here for biobank-scale WGS analysis provide a useful complement to studying repeat instability in families and in patient cohorts using targeted sequencing techniques,” they noted. Combining these approaches should provide opportunities for further discovery.
