A phenome-wide association study of genetically determined nicotine metabolism reveals novel links with health-related outcomes.

ABSTRACT: Faster nicotine metabolism, defined as the nicotine metabolite ratio (NMR), is known to associate with heavier smoking and challenges in smoking cessation. However, the broader health implications of genetically determined nicotine metabolism are not well characterized. We performed a hypothesis-free phenome-wide association study (PheWAS) of over 21,000 outcome variables from UK Biobank (UKB) to explore how the NMR (measured as the 3-hydroxycotinine-to-cotinine ratio) associates with the phenome. As the exposure variable, we used a genetic score for faster nicotine metabolism based on 10 putative causal genetic variants, explaining 33.8 % of the variance in the NMR. We analysed ever and never smokers separately to assess whether a causal pathway through nicotine metabolism is plausible. A

SUBMITTER: Buchwald J 

PROVIDER: S-EPMC12537601 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature