Shuai Yuan1, Dipender Gill2, Edward L Giovannucci3, Susanna C Larsson4. 1. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 2. Department of Biostatistics and Epidemiology, School of Public Health, Imperial College London, London, United Kingdom; Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education and Institute for Infection and Immunity, St George's, University of London, London, United Kingdom; Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George's University Hospitals NHS Foundation Trust, London, United Kingdom; Novo Nordisk Research Centre Oxford, Oxford, United Kingdom. 3. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: susanna.larsson@ki.se.
Abstract
BACKGROUND & AIMS: Obesity, type 2 diabetes, and lifestyle factors (cigarette smoking, alcohol drinking, and coffee consumption) have been associated with the risk of developing gallstone disease in observational studies, but whether these associations are causal is undetermined. We conducted a Mendelian randomization study to assess these associations. METHODS: Genetic instruments associated with the exposures at the genome-wide significance (p < 5×10-8) level were selected from corresponding genome-wide association studies (n=224 459 to 1 232 091 individuals). Summary-level data for gallstone disease were obtained from the UK Biobank (10 520 cases and 350 674 non-cases) and FinnGen consortium (11 675 cases and 121 348 non-cases). Univariable and multivariable Mendelian randomization analyses were conducted. Results from UK Biobank and FinnGen were combined using fixed-effects meta-analysis. RESULTS: The odds ratios were 1.63 (95% confidence interval (CI), 1.49, 1.79) for one standard deviation (SD) increase in body mass index, 1.81 (95% CI, 1.60, 2.05) for one SD increase in waist circumference, 1.13 (95% CI, 1.09, 1.17) for one unit increase in the log-odds ratio of type 2 diabetes and 1.25 (95% CI, 1.16, 1.34) for one SD increase in prevalence of smoking initiation. The associations for body mass index and type 2 diabetes persisted after mutual adjustment. Genetically predicted coffee consumption was inversely associated with gallstone disease after adjustment for body mass index and smoking (odds ratio per 50% increase 0.44, 95% CI, 0.21, 0.91). There was no association with alcohol consumption. CONCLUSIONS: This study supports independent causal roles of obesity, type 2 diabetes, and smoking in gallstone disease.
BACKGROUND & AIMS: Obesity, type 2 diabetes, and lifestyle factors (cigarette smoking, alcohol drinking, and coffee consumption) have been associated with the risk of developing gallstone disease in observational studies, but whether these associations are causal is undetermined. We conducted a Mendelian randomization study to assess these associations. METHODS: Genetic instruments associated with the exposures at the genome-wide significance (p < 5×10-8) level were selected from corresponding genome-wide association studies (n=224 459 to 1 232 091 individuals). Summary-level data for gallstone disease were obtained from the UK Biobank (10 520 cases and 350 674 non-cases) and FinnGen consortium (11 675 cases and 121 348 non-cases). Univariable and multivariable Mendelian randomization analyses were conducted. Results from UK Biobank and FinnGen were combined using fixed-effects meta-analysis. RESULTS: The odds ratios were 1.63 (95% confidence interval (CI), 1.49, 1.79) for one standard deviation (SD) increase in body mass index, 1.81 (95% CI, 1.60, 2.05) for one SD increase in waist circumference, 1.13 (95% CI, 1.09, 1.17) for one unit increase in the log-odds ratio of type 2 diabetes and 1.25 (95% CI, 1.16, 1.34) for one SD increase in prevalence of smoking initiation. The associations for body mass index and type 2 diabetes persisted after mutual adjustment. Genetically predicted coffee consumption was inversely associated with gallstone disease after adjustment for body mass index and smoking (odds ratio per 50% increase 0.44, 95% CI, 0.21, 0.91). There was no association with alcohol consumption. CONCLUSIONS: This study supports independent causal roles of obesity, type 2 diabetes, and smoking in gallstone disease.
Authors: Susan Martin; Jessica Tyrrell; E Louise Thomas; Matthew J Bown; Andrew R Wood; Robin N Beaumont; Lam C Tsoi; Philip E Stuart; James T Elder; Philip Law; Richard Houlston; Christopher Kabrhel; Nikos Papadimitriou; Marc J Gunter; Caroline J Bull; Joshua A Bell; Emma E Vincent; Naveed Sattar; Malcolm G Dunlop; Ian P M Tomlinson; Sara Lindström; Jimmy D Bell; Timothy M Frayling; Hanieh Yaghootkar Journal: Elife Date: 2022-01-25 Impact factor: 8.713
Authors: Junghyun Lim; Janine Wirth; Kana Wu; Edward Giovannucci; Peter Kraft; Constance Turman; Mingyang Song; Manol Jovani; Andrew T Chan; Amit D Joshi Journal: Clin Gastroenterol Hepatol Date: 2021-07-02 Impact factor: 13.576