Back to Search Results

Lifestyle and metabolic factors for nonalcoholic fatty liver disease: Mendelian randomization study.

Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobelsväg 13, 17177, Stockholm, Sweden. Centre for Global Health, Zhejiang University School of Medicine, Hangzhou, China. Department of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, China. School of Public Health and the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK. Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada. Department of Medicine, Faculty of Medicine, Université Laval, Quebec, QC, Canada. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. Clinical Pharmacology and Therapeutics Section, Institute for Infection and Immunity, St George's, University of London, London, UK. Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George's University Hospitals NHS Foundation Trust, London, UK. Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford, UK. Department of Epidemiology, Harvard T H Chan School of Public Health, Boston, MA, USA. Department of Nutrition, Harvard T H Chan School of Public Health, Boston, MA, USA. Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobelsväg 13, 17177, Stockholm, Sweden. susanna.larsson@ki.se. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. susanna.larsson@ki.se.

European journal of epidemiology. 2022;(7):723-733
Full text from:

Other resources

Abstract

The risk factors for nonalcoholic fatty liver disease (NAFLD) have not been clearly identified. We conducted a Mendelian randomization (MR) study to explore this. Independent genetic variants strongly associated with 5 lifestyle and 9 metabolic factors were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for NAFLD were obtained from a GWAS meta-analysis of 8434 cases and 770,180 non-cases (discovery dataset) and another GWAS meta-analysis of 1483 cases and 17,781 non-cases (replication dataset). Univariable and multivariable MR analyses were performed. There were associations with NAFLD for lifetime smoking index (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.31-1.93 per SD-increase), body mass index (BMI, OR 1.33, 95% CI 1.23-1.43 per SD-increase), waist circumference (OR 1.82; 95% CI 1.48-2.24 per SD-increase), type 2 diabetes (OR 1.21, 95% CI 1.15-1.27 per unit increase in log-transformed odds), systolic blood pressure (OR 1.17; 95% CI 1.07-1.26 per 10 mmHg increase), high-density lipoprotein cholesterol (OR 0.84, 95% CI 0.77-0.90 per SD-increase), and triglycerides (OR 1.23, 95% CI 1.15-1.33 per SD-increase). The associations for type 2 diabetes, systolic blood pressure, triglycerides, but not for high-density lipoprotein cholesterol remained strong after adjusting for genetically-predicted BMI. Genetic liability to type 2 diabetes mediated 51.4% (95% CI 13.4-89.3%) of the BMI-effects on NAFLD risk. There were suggestive inverse associations of genetically-predicted alcohol, coffee, and caffeine consumption, and vigorous physical activity with NAFLD risk. This study identified several lifestyle and metabolic factors that may be causally implicated in NAFLD.

Methodological quality

Publication Type : Meta-Analysis

Metadata