Genetic Evidence Links Substance Use to Faster Biological Aging

Mendelian randomization analyses found significant causal effects of genetic predisposition to tobacco use disorder and smoking quantity on markers of biological, physical, and cognitive aging. Causal effects of problematic alcohol use and cannabis use disorder were also detected but with mixed results across different aging markers. Evidence of reverse causality (aging causing substance use) was minimal.

Researchers used genome-wide association study data (sample sizes from 28K to 2.7M) to test genetic correlations between substance use and aging metrics using LDSC regression. Mendelian randomization was then used to assess causal relationships between genetic predisposition to substance use and various aging indices.

This study uses genetic methods to move beyond correlation and test whether substance use actually causes accelerated aging. The approach helps disentangle whether substance users age faster because of their use or because of shared underlying factors.

While tobacco's effect on aging is well established, this genetic approach provides some of the first causal evidence that cannabis use disorder may also contribute to accelerated biological aging, though the evidence is weaker and less consistent than for tobacco.

Mendelian randomization assumes genetic instruments affect aging only through substance use, which may not always hold. Cannabis use disorder GWAS sample sizes are smaller than for tobacco or alcohol. Most data comes from European ancestry populations.