| Title: | Serum biomarkers are altered in UK Biobank participants with mosaic chromosomal alterations |
| Journal: | Human Molecular Genetics |
| Published: | 11 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37565819/ |
| DOI: | https://doi.org/10.1093/hmg/ddad133 |
| URL: | https://academic.oup.com/hmg/advance-article-pdf/doi/10.1093/hmg/ddad133/51098543/ddad133.pdf |
Publication 9761
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Abstract
Age-related clonal expansion of cells harbouring mosaic chromosomal alterations (mCAs) is one manifestation of clonal haematopoiesis. Identifying factors that influence the generation and promotion of clonal expansion of mCAs are key to investigate the role of mCAs in health and disease. Herein, we report on widely measured serum biomarkers and their possible association with mCAs, which could provide new insights into molecular alterations that promote acquisition and clonal expansion. We performed a cross-sectional investigation of the association of 32 widely measured serum biomarkers with autosomal mCAs, mosaic loss of the Y chromosome, and mosaic loss of the X chromosome in 436 784 cancer-free participants from the UK Biobank. mCAs were associated with a range of commonly measured serum biomarkers such as lipid levels, circulating sex hormones, blood sugar homeostasis, inflammation and immune function, vitamins and minerals, kidney function, and liver function. Biomarker levels in participants with mCAs were estimated to differ by up to 5% relative to mCA-free participants, and individuals with higher cell fraction mCAs had greater deviation in mean biomarker values. Polygenic scores associated with sex hormone binding globulin, vitamin D, and total cholesterol were also associated with mCAs. Overall, we observed commonly used clinical serum biomarkers related to disease risk are associated with mCAs, suggesting mechanisms involved in these diseases could be related to mCA proliferation and clonal expansion.</p>
7 Authors
- Aubrey K Hubbard
- Derek W Brown
- Weiyin Zhou
- Shu-Hong Lin
- Giulio Genovese
- Stephen J Chanock
- Mitchell J Machiela
1 Application
| Application ID | Title |
|---|---|
| 21552 | Detection of large-scale copy-number and copy-neutral mosaic alterations in circulating leukocyte DNA of UK Biobank cancer cases and cancer-free controls |
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