| Title: | Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease |
| Journal: | BMC Medicine |
| Published: | 11 Jun 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38862964/ |
| DOI: | https://doi.org/10.1186/s12916-024-03466-0 |
| URL: | https://bmcmedicine.biomedcentral.com/counter/pdf/10.1186/s12916-024-03466-0 |
Publication 11873
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Abstract
BackgroundMitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored.MethodsWe extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality.Results96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value < 8.21e − 07. The coding genes of these PTVs were mainly enriched in pathways related to lipid, fatty acid, amino acid, and carbohydrate metabolisms. The 866 PTVs were presented in 1.07% (4721) of participants. Compared with participants who did not carry any of the PTVs, the carriers had a 5.33-fold (95% CI 4.15-6.85), 2.82-fold (1.69-4.72), and 4.41-fold (3.04-6.41) increased risk for fibrosis and cirrhosis of liver, liver cancer, and liver disease-related mortality, respectively. These adverse effects were consistent across subgroups based on age, sex, body mass index, smoking status, and presence of hypertension, diabetes, dyslipidemia, and metabolic syndrome.ConclusionsOur findings revealed a significant impact of PTVs in MT-related genes on liver disease risk, highlighting the importance of these variants in identifying populations at risk of liver diseases and facilitating early clinical interventions.</p>
13 Keywords
- Adult
- Aged
- Chronic Disease
- Exome Sequencing
- Female
- Genes, Mitochondrial
- Genetic Predisposition to Disease
- Genetic Variation
- Humans
- Liver Diseases
- Male
- Middle Aged
- United Kingdom
8 Authors
- Huangbo Yuan
- Zhenqiu Liu
- Mingyang Chen
- Qiaoyi Xu
- Yanfeng Jiang
- Tiejun Zhang
- Chen Suo
- Xingdong Chen
1 Application
| Application ID | Title |
|---|---|
| 92718 | Deciphering chronic disease - association studies of genome, exposome and phenome |
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