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Smoking reduces plasma bilirubin: Observational and genetic analyses in the Copenhagen General Population Study

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Introduction: Observational studies have found lower concentrations of plasma bilirubin in current smokers compared to former and never smokers. However, whether there is a causal relationship between smoking and bilirubin is unknown. In a Mendelian randomisation analysis, we tested the hypothesis that higher tobacco consumption is causally associated with lower concentrations of plasma bilirubin.

Methods: We genotyped 103 557 individuals aged 20-100 years from the Copenhagen General Population Study for the CHRNA3 rs1051730 genotype, known to be associated with higher tobacco consumption. Tobacco consumption was defined as daily and cumulative tobacco consumption.

Results: In observational multivariable adjusted analyses, a 10 g/day higher daily tobacco consumption was associated with a 0.28 µmol/L (95% confidence interval: 0.20-0.35) lower concentration of plasma bilirubin in current smokers and a 10 pack-year higher cumulative smoking was associated with a 0.19 µmol/L (0.17-0.21) lower concentration of plasma bilirubin in former and current smokers. Using the CHRNA3 rs1051730 genotype as a proxy for daily and cumulative tobacco consumption, the difference in plasma bilirubin per T-allele was -0.12 µmol/L (-0.23 to -0.002) in current smokers and -0.09 µmol/L (-0.15 to -0.01) in current and former smokers combined. Furthermore, observationally bilirubin concentrations increased with time from smoking cessation in former smokers.

Conclusion: Higher daily and cumulative tobacco consumption were associated with lower concentrations of plasma bilirubin in observational and genetic analyses, suggesting that the association is causal.

Original languageEnglish
JournalNicotine & Tobacco Research
Pages (from-to)104-110
ISSN1462-2203
DOIs
Publication statusPublished - Jan 2020

ID: 56612675