The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study
| Autor: | Anu Loukola, George Davey Smith, Amy E Taylor, Caroline L Relton, Rebecca C Richmond, Jaakko Kaprio, Teemu Palviainen, Marcus R. Munafò |
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| Přispěvatelé: | Institute for Molecular Medicine Finland, Helsinki Institute of Life Science HiLIFE, HUSLAB, Department of Public Health, Clinicum, Genetic Epidemiology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Longitudinal study medicine.medical_treatment Genome-wide association study Brain and Behaviour Body Mass Index Nicotine Cohort Studies chemistry.chemical_compound 0302 clinical medicine Risk Factors 030212 general & internal medicine Longitudinal Studies ASSOCIATIONS 2. Zero hunger DISSATISFACTION 0303 health sciences Tobacco and Alcohol Smoking 1184 Genetics developmental biology physiology Mendelian Randomization Analysis Middle Aged 3. Good health BIAS OBESITY Female Physical and Mental Health Mendelian randomisation analysis General Article ICEP body mass index procedure medicine.drug Adult WEIGHT CONTROL BEHAVIORS Polymorphism Single Nucleotide 03 medical and health sciences Mendelian randomization medicine Humans 030304 developmental biology business.industry Body Weight DNA Methylation chemistry COTININE LEVELS 1182 Biochemistry cell and molecular biology Smoking cessation Smoking Cessation CIGARETTE-SMOKING CESSATION GAIN Cotinine business Body mass index metabolism Demography Genome-Wide Association Study |
| Zdroj: | Taylor, A E, Richmond, R C, Palviainen, T, Loukola, A, Wootton, R E, Kaprio, J, Relton, C L, Davey Smith, G & Munafò, M R 2019, ' The effect of body mass index on smoking behaviour and nicotine metabolism : a Mendelian randomization study ', Human Molecular Genetics, vol. 28, no. 8, ddy434, pp. 1322-1330 . https://doi.org/10.1093/hmg/ddy434 Human Molecular Genetics |
| DOI: | 10.1101/299834 |
| Popis: | BackgroundGiven clear evidence that smoking lowers weight, it is possible that individuals with higher body mass index (BMI) smoke in order to lose or maintain their weight.Methods and FindingsWe undertook Mendelian randomization analyses using 97 genetic variants associated with BMI. We performed two sample Mendelian randomization analyses of the effects of BMI on smoking behaviour in UK Biobank (N=335,921) and the Tobacco and Genetics consortium genomewide association study (GWAS) (N≤74,035) respectively, and two sample Mendelian randomization analyses of the effects of BMI on cotinine levels (N≤4,548) and nicotine metabolite ratio (N≤1,518) in published GWAS, and smoking-related DNA methylation in the Avon Longitudinal Study of Parents and Children (N≤846).In inverse variance weighted Mendelian randomization analysis, there was evidence that higher BMI was causally associated with smoking initiation (OR for ever vs never smoking per one SD increase in BMI: 1.19, 95% CI: 1.11 to 1.27) and smoking heaviness (1.45 additional cigarettes smoked per day per SD increase in BMI, 95% CI: 1.03 to 1.86), but little evidence for a causal effect with smoking cessation. Results were broadly similar using pleiotropy robust methods (MR-Egger, median and weighted mode regression). These results were supported by evidence for a causal effect of BMI on DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) locus. There was no strong evidence that BMI was causally associated with cotinine, but suggestive evidence for a causal negative association with the nicotine metabolite ratio.ConclusionsThere is a causal bidirectional association between BMI and smoking, but the relationship is likely to be complex due to opposing effects on behaviour and metabolism. It may be useful to consider BMI and smoking together when designing prevention strategies to minimise the effects of these risk factors on health outcomes. |
| Databáze: | OpenAIRE |
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