Interaction between genetic predisposition, smoking, and dementia risk: a population-based cohort study
Na Zhang1,2, Janice M Ranson3, Zhi-Jie Zheng1,2
1Department of Global Health, Peking University School of Public Health, Beijing, China.
Scientific Reports
|June 22, 2021
Summary
Cigarette smoking increases dementia risk, especially for those with specific apolipoprotein E (APOE) gene variations. Genetic predisposition, particularly APOE genotype, modifies smoking
Area of Science:
- Neuroscience and Genetics
- Public Health and Epidemiology
Background:
- Cigarette smoking is a known risk factor for dementia.
- Genetic factors, including apolipoprotein E (APOE) genotype and polygenic risk scores, may influence dementia susceptibility.
- The interplay between smoking, genetic predisposition, and dementia risk requires further investigation.
Purpose of the Study:
- To investigate whether the association between cigarette smoking and dementia risk is modified by genetic factors.
- To examine the specific roles of apolipoprotein E (APOE) genotype and polygenic risk scores in this interaction.
- To determine if genetic predisposition alters the impact of smoking on dementia development.
Main Methods:
- Utilized data from 193,198 UK Biobank participants aged 60-73 years without dementia at baseline.
- Assessed dementia risk in relation to current smoking status, stratified by APOE genotype (non-carriers, one ε4 allele, two ε4 alleles) and polygenic risk.
- Employed Cox proportional hazards models to calculate adjusted hazard ratios and tested for interactions between genetic factors and smoking status.
Main Results:
- A significant interaction was observed between APOE genotype and smoking status (P=0.002), indicating that APOE influences smoking's effect on dementia.
- Current smokers with two APOE-ε4 alleles showed a higher dementia incidence compared to never smokers, though the interaction was not statistically significant in this subgroup.
- No significant interaction was found between polygenic risk scores (excluding APOE region) and smoking status (P=0.25), suggesting polygenic risk does not modify smoking's impact on dementia.
Conclusions:
- APOE genotype, but not polygenic risk, significantly modifies the association between cigarette smoking and dementia risk.
- Individuals with specific APOE genotypes may experience a differential impact of smoking on their likelihood of developing dementia.
- These findings highlight the importance of considering genetic background when assessing smoking-related dementia risks.
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