New research has found a larger group of genes that are involved in clonal haematopoiesis than previously believed. This discovery has significant implications for both disease and diagnostic tests.
The scientists have uncovered 17 more genes that contribute to the abnormal overgrowth of mutated blood cells as we get older. The study, which was published in Nature Genetics, offers a more comprehensive understanding of the genetic factors that play a role in clonal haematopoiesis.The process associated with getting older and connected to higher chances of blood cancers is being investigated by a team of scientists. The researchers analyzed sequencing data from more than 200,000 people in the UK Biobank cohort to look for genes that show signs of “positive selection,” meaning mutations that allow mutant cell populations to expand significantly over time. They found 17 new genes that have similar disease associations as known clonal haematopoiesis mutations, underscoring their importance in the accumulation of mutant blood cell populations.By identifying these previously unknown genetic factors, the study provides new opportunities to investigate the molecular processes behind clonal hematopoiesis and its impact on disease progression, ultimately leading to improved methods for promoting healthy aging. Furthermore, this could result in more effective genetic screenings to gauge the likelihood of developing blood cancers and cardiovascular ailments. As we grow older, our cells amass arbitrary genetic changes. A portion of these alterations can furnish a competitive growth edge, enabling mutated cells to proliferate and surpass the healthy cells, forming sizable ‘clones’ or groupings of identical mutant cells.When blood stem cells undergo this process of positive selection, it is referred to as clonal haematopoiesis, which has been connected to various diseases such as blood cancers and cardiovascular disease that are related to aging. Although approximately 70 genes have been previously identified as being associated with clonal haematopoiesis, recent cases have not shown mutations in these known driver genes, indicating the potential involvement of other genetic factors. To better understand this, researchers aimed to identify the specific patterns of positive selection in the aging blood system by utilizing data from whole exome sequencing of over 200,000 individuals.Individuals in the UK Biobank cohort were studied, and researchers discovered 17 genes that contribute to the growth of mutant cell clones in the blood, expanding the known set of drivers.
The inclusion of mutations in these newly identified genes resulted in an 18% increase in the prevalence of clonal haematopoiesis in the UK Biobank cohort, highlighting their impact on the aging process.
Dr. Michael Spencer Chapman, a co-first author of the study at the Wellcome Sanger Institute, noted that while current genetic tests have been useful for early disease detection, there is potential to enhance them further by incorporating these 17 additional genes associated with clonal haematopoiesis.The study revealed that by improving genetic testing methods, we can better detect risks of blood cancers and cardiovascular diseases associated with extra-medullary hematopoiesis. Nick Bernstein, the co-first author of the study, stated that the newly identified genes provide a more comprehensive understanding of strategies to delay or reverse abnormal mutant cell overgrowths in the blood. These genes appear to impact inflammation and immunity, which are significant factors in conditions such as heart disease and strokes. Although interventions based on this research are still in the early stages, this discovery is a step towards promoting healthier aging.The study from the Wellcome Sanger Institute and the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge has revealed a wide range of genes that contribute to the accumulation of mutant blood cell clones with age. Dr. Jyoti Nangalia, the senior author of the study, believes that this discovery opens up possibilities for future treatments across a wide range of diseases. However, she also emphasizes the need for larger studies across diverse populations to identify remaining driver genes and provide further insights into this process and disease links.
