Nordestgaard, B. | bioRxiv Science

bioRxiv2018

Appraising the causal relevance of DNA methylation for risk of lung cancer

DNA methylation changes in peripheral blood have been identified in relation to lung cancer risk. However, the causal nature of these associations remains to be fully elucidated. Meta-analysis of four epigenome-wide association studies (918 cases, 918 controls) revealed differential methylation at 16 CpG sites (FDR < 0.05) in relation to lung cancer risk. A two-sample Mendelian randomization analysis, using genetic instruments for methylation at 14 of the 16 CpG sites, and 29,863 cases and 55,586 controls from the TRICL-ILCCO lung cancer consortium, was performed to appraise the causal role of methylation at these sites on lung cancer. This approach provided little evidence that DNA methylation in peripheral blood at the 14 CpG sites play a causal role in lung cancer development, including for cg05575921 AHRR, where methylation is strongly associated with lung cancer risk. Further studies are needed to investigate the causal role played by DNA methylation in lung tissue.

epidemiology↗

bioRxiv2017

Cigarette smoking increases coffee consumption: findings from a Mendelian randomisation analysis

BackgroundSmokers tend to consume more coffee than non-smokers and there is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases the metabolism of caffeine, so this association may represent a causal effect of smoking on caffeine intake.\n\nMethodsWe performed a Mendelian randomisation analysis in 114,029 individuals from the UK Biobank, 56,664 from the Norwegian HUNT study and 78,650 from the Copenhagen General Population Study. We used a genetic variant in the CHRNA5 nicotinic receptor (rs16969968) as a proxy for smoking heaviness. Coffee and tea consumption were self-reported. Analyses were conducted using linear regression and meta-analysed across studies.\n\nResultsEach additional cigarette per day consumed by current smokers was associated with higher coffee consumption (0.10 cups per day, 95% CI:0.03,0.17). There was weak evidence for an increase in tea consumption per additional cigarette smoked per day (0.04 cups per day, 95% CI:-0.002,0.07). There was strong evidence that each additional copy of the minor allele of rs16969968 (which increases daily cigarette consumption) in current smokers was associated with higher coffee consumption (0.15 cups per day, 95% CI:0.11,0.20), but only weak evidence for an association with tea consumption (0.04 cups per day, 95% CI:- 0.01,0.09). There was no clear evidence that rs16969968 was associated with coffee or tea consumption in never or former smokers.\n\nConclusionThese findings suggest that higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but may also reflect behavioural links between smoking and coffee.

genetics↗