| Title: | Genetic risk amplifies lifestyle effects on hepatic steatosis and its progression: Insights from a population-based cohort |
| Journal: | Digestive and Liver Disease |
| Published: | 20 Jan 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39837741/ |
| DOI: | https://doi.org/10.1016/j.dld.2025.01.040 |
Publication 14900
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Abstract
BACKGROUND: Steatotic liver disease (SLD) is influenced by both genetics and lifestyle factors, with lifestyle effects varying by genetic susceptibility. We aimed to evaluate gene-lifestyle interactions on SLD risk.</p>
METHODS: We included 28,215 UK Biobank participants with available data. Predictors were healthy lifestyle patterns, PNPLA3-rs738409, TM6SF2-rs58542926, a 16-variant hepatic steatosis polygenic risk score (PRS), and gene-environment interactions. Primary outcome was liver fat content (LFC); secondary outcomes were cT1 (a measure of liver inflammation/fibrosis) and SLD-related events.</p>
RESULTS: Lifestyle predictors, except smoking, reduced LFC, while genetic predictors increased it. Genetic predictors significantly interacted with healthy lifestyle patterns, sedentary behavior and social connection. Lifestyle effects on lower LFC were up to 6.3-fold stronger in PNPLA3-rs738409-GG vs. -CC individuals, and 1.5-7.0 times higher in the top vs. bottom PRS quartile. PRS and PNPLA3 also interacted with alcohol consumption, diet, and PNPLA3 further interacted with physical activity. These interactions were more pronounced in overweight participants. Genetic factors and physical activity interacted to influence cT1, while PRS, PNPLA3 and sleep duration were associated with cardiovascular events.</p>
CONCLUSIONS: Lifestyle effects on LFC, cT1 and cardiovascular events were accentuated in individuals at higher SLD genetic risk, implying lifestyle interventions may be more impactful in these populations.</p>
23 Keywords
- Adult
- Aged
- Alcohol Drinking
- Cohort Studies
- Diet
- Disease Progression
- Exercise
- Fatty Liver
- Female
- Gene-Environment Interaction
- Genetic Predisposition to Disease
- Genetic Risk Score
- Healthy Lifestyle
- Humans
- Liver
- Male
- Middle Aged
- Risk Assessment
- Risk Factors
- Sleep
- Social Behavior
- UK Biobank
- United Kingdom
7 Authors
- Xin Zhang
- Haili Wang
- Chengnan Guo
- Shuzhen Zhao
- Yi Li
- Zhenqiu Liu
- Tiejun Zhang
1 Application
| Application ID | Title |
|---|---|
| 92718 | Deciphering chronic disease - association studies of genome, exposome and phenome |
Enabling scientific discoveries that improve human health