Analysis of somatic mutations in whole blood from 200,618 individuals identifies pervasive positive selection and novel drivers of clonal hematopoiesis
- Calico Life Sciences LLC, South San Francisco, CA, USA
- Wellcome Sanger Institute, Hinxton, UK
- Wellcome-MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK
Why did they do this study?
The study aimed to understand the genetic basis and implications of clonal hematopoiesis (CH) by analyzing somatic mutations in whole blood. CH is associated with aging and an increased risk of haematological malignancies, cardiovascular disease, and overall mortality. The goal was to identify novel genetic drivers of CH and understand their impact on health.
How did they do it?
Researchers analysed exome sequencing data from 200,618 individuals in the UK Biobank, focusing on somatic mutations in whole blood. They identified genes under positive selection by comparing non-synonymous (protein-altering) and synonymous (non-altering) mutations. The findings were validated using whole-genome sequencing of single-cell-derived hematopoietic colonies from 10,837 individuals.
What did they find out?
The study identified 17 novel genes under positive selection associated with CH, such as ZBTB33, CHEK2, and MYD88. Mutations in these genes increased in frequency with age and were linked to higher risks of infection, death, and hematological malignancies. These findings highlight the importance of these additional genes in the aging process and their potential role in health outcomes.