| Title: | Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis |
| Journal: | Journal of Clinical and Translational Hepatology |
| Published: | 28 May 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38974956/ |
| DOI: | https://doi.org/10.14218/jcth.2023.00575 |
| URL: | ~Ehttps://publinestorage.blob.core.windows.net/journals/JCTH.2023.0(0).0.00575.Xinyuan Ge.pdf~ |
Publication 11971
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Abstract
Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction.</p>
Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk.</p>
Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09-3.78] vs. 1.14 [0.80-1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41-12.07]).</p>
Conclusions: The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.</p>
15 Authors
- Xinyuan Ge
- Lu Zhang
- Maojie Liu
- Xiao Wang
- Xin Xu
- Yuqian Yan
- Chan Tian
- Juan Yang
- Yang Ding
- Chengxiao Yu
- Jing Lu
- Longfeng Jiang
- Qiang Wang
- Qun Zhang
- Ci Song
1 Application
| Application ID | Title |
|---|---|
| 64689 | Associations of genetic factors, healthy lifestyle behavior, testosterone level and sleep traits with human healthspan |
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