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Bjorngaard, J. H., Gunnell, D., Elvestad, M. B., Davey Smith, G., Skorpen, F., Krokan, H., et al. (2013). The causal role of smoking in anxiety and depression: a Mendelian randomization analysis of the HUNT study. Psychol Med, 43(4), 711–719.
Abstract: BACKGROUND: Cigarette smoking is strongly associated with mental illness but the causal direction of the association is uncertain. We investigated the causal relationship between smoking and symptoms of anxiety and depression in the Norwegian HUNT study using the rs1051730 single nucleotide polymorphism (SNP) variant located in the nicotine acetylcholine receptor gene cluster on chromosome 15 as an instrumental variable for smoking phenotypes. Among smokers, this SNP is robustly associated with smoking quantity and nicotine dependence. Method In total, 53 601 participants were genotyped for the rs1051730 SNP and provided information on smoking habits and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS). RESULTS: Self-reported smoking was positively associated with the prevalence of both anxiety and depression, and the measured polymorphism was positively associated with being a current smoker and the number of cigarettes smoked in current smokers. In the sample as a whole, risk of anxiety increased with each affected T allele [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02-1.09, p = 0.002] but there was no association with depression (p = 0.31). However, we found no clear association of the polymorphism with either anxiety (OR 1.03, 95% CI 0.97-1.09, p = 0.34) or depression (OR 1.02, 95% CI 0.95-1.09, p = 0.62) among smokers. CONCLUSIONS: As there was no association of the smoking-related rs1051730 SNP with anxiety and depression among smokers, the results suggest that smoking is not a cause of anxiety and depression.
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Bjorngaard, J. H., Nordestgaard, A. T., Taylor, A. E., Treur, J. L., Gabrielsen, M. E., Munafo, M. R., et al. (2017). Heavier smoking increases coffee consumption: findings from a Mendelian randomization analysis. Int J Epidemiol, .
Abstract: Background: There is evidence for a positive relationship between cigarette and coffee consumption in smokers. Cigarette smoke increases metabolism of caffeine, so this may represent a causal effect of smoking on caffeine intake. Methods: We performed Mendelian randomization analyses in the UK Biobank ( N = 114 029), the Norwegian HUNT study ( N = 56 664) and the Copenhagen General Population Study (CGPS) ( N = 78 650). We used the rs16969968 genetic variant as a proxy for smoking heaviness in all studies and rs4410790 and rs2472297 as proxies for coffee consumption in UK Biobank and CGPS. Analyses were conducted using linear regression and meta-analysed across studies. Results: Each 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 (0.16 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 or that the coffee-related variants were associated with cigarette consumption. Conclusions: Higher cigarette consumption causally increases coffee intake. This is consistent with faster metabolism of caffeine by smokers, but could also reflect a behavioural effect of smoking on coffee drinking.
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Machiela, M. J., Hofmann, J. N., Carreras-Torres, R., Brown, K. M., Johansson, M., Wang, Z., et al. (2017). Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma. Eur Urol, 72(5), 747–754.
Abstract: BACKGROUND: Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. OBJECTIVE: We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. DESIGN, SETTING, AND PARTICIPANTS: Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. RESULTS AND LIMITATIONS: Longer genetically inferred telomere length was associated with an increased risk of RCC (OR=2.07 per predicted kilobase increase, 95% confidence interval [CI]:=1.70-2.53, p<0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R(2)>0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR=1.73, 95% CI=1.36-2.21, p<0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N=5573, OR=1.93, 95% CI=1.50-2.49, p<0.0001), papillary (N=573, OR=1.96, 95% CI=1.01-3.81, p=0.046), and chromophobe RCC (N=203, OR=2.37, 95% CI=0.78-7.17, p=0.13). CONCLUSIONS: Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. PATIENT SUMMARY: Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma.
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