Publication date: Jul 04, 2025
Smoking represents the largest preventable risk factor for human health, yet previous studies have failed to establish conclusive evidence regarding the causal relationship between smoking and neurodegenerative diseases. This study employs genetic correlation and Mendelian randomization analyses to investigate the potential association between smoking and neurodegenerative disorders. This study analyzed summary data from genome-wide association studies (GWAS) on smoking and neurodegenerative diseases. Genetic correlations were evaluated using linkage disequilibrium score regression (LDSC), and causal relationships were assessed through multiple Mendelian randomization methods including inverse-variance weighted (IVW), MR-Egger regression, weighted median (WME), weighted mode (WM), and simple mode (SM). sensitivity analyses were performed to examine heterogeneity, horizontal pleiotropy, and conduct leave-one-out analysis. whether an individual had ever smoked regularly (SmkInit) is positively correlated with an increased risk of Alzheimer’s disease (AD) (rg = 0. 134, P = 2. 74 cD7 10⁻⁸) and negatively correlated with the risk of Parkinson’s disease (PD) (rg = - 0. 100, P = 1. 8 cD7 10⁻). cigarettes per day (CigDay) are associated with a higher risk of AD (rg = 0. 162, P = 4. 26 cD7 10⁻⁵). Smoking cessation (SmkCes) is linked to an elevated risk of AD (rg = 0. 1466, P = 1. 5 cD7 10⁻), whereas age of initiation of regular smoking (AgeSmk) is negatively correlated with AD risk (rg = - 0. 181, P = 8. 63 cD7 10⁻⁶) but positively correlated with PD risk (rg = 0. 170, P = 2. 0 cD7 10⁻). Results suggest that both SmkInit and CigDay significantly increase AD risk (OR = 1. 030, P = 1. 74 cD7 10⁻⁴; OR = 1. 022, P = 5. 04 cD7 10⁻⁴), while SmkCes is associated with a reduced risk of PD (OR = 0. 638, P = 1. 91 cD7 10⁻⁶) and amyotrophic lateral sclerosis (ALS) (OR = 0. 830, P = 5. 29 cD7 10⁻⁶). This study identified significant genetic associations between smoking behaviors and neurodegenerative diseases. CigDay and SmkInit increased AD risk, while SmkCes was linked to reduced risks of PD and ALS.
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| Concepts | Keywords |
|---|---|
| Alzheimer | Alzheimer’s disease |
| Amyotrophic | Amyotrophic lateral sclerosis |
| Cigarettes | Genetic correlation |
| Mendelian randomization | |
| Neurodegenerative diseases | |
| Parkinson’s disease | |
| Smoking |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | neurodegenerative diseases |
| pathway | REACTOME | Neurodegenerative Diseases |
| disease | MESH | Alzheimer’s disease |
| disease | MESH | Parkinson’s disease |
| disease | MESH | amyotrophic lateral sclerosis |
| pathway | KEGG | Amyotrophic lateral sclerosis |
| pathway | REACTOME | Reproduction |
| disease | MESH | lateral sclerosis |
| disease | MESH | multiple sclerosis |
| disease | MESH | dementia |
| disease | MESH | Lewy body dementia |
| pathway | REACTOME | Methylation |
| disease | MESH | oxidative stress |
| disease | MESH | pathogenesis |
| disease | MESH | psychological well being |
| drug | DRUGBANK | Coenzyme M |
| drug | DRUGBANK | Indoleacetic acid |
| drug | DRUGBANK | Ranitidine |
| drug | DRUGBANK | L-Phenylalanine |
| disease | MESH | cognitive impairment |
| disease | MESH | neuroinflammation |
| pathway | REACTOME | Metabolism |
| disease | MESH | abnormalities |
| disease | MESH | atrophy |
| disease | MESH | tic |
| drug | DRUGBANK | Oxygen |
| drug | DRUGBANK | Nitrogen |
| drug | DRUGBANK | Nicotine |
| drug | DRUGBANK | Dopamine |