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Open Access 30-04-2022 | Fatty Liver | HEPATIC EPIDEMIOLOGY

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

Authors: Shuai Yuan, Jie Chen, Xue Li, Rongrong Fan, Benoit Arsenault, Dipender Gill, Edward L. Giovannucci, Ju-sheng Zheng, Susanna C. Larsson

Published in: European Journal of Epidemiology | Issue 7/2022

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.

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Title: Lifestyle and metabolic factors for nonalcoholic fatty liver disease: Mendelian randomization study
Authors: Shuai Yuan
Jie Chen
Xue Li
Rongrong Fan
Benoit Arsenault
Dipender Gill
Edward L. Giovannucci
Ju-sheng Zheng
Susanna C. Larsson
Publication date: 30-04-2022
Publisher: Springer Netherlands
Keywords: Fatty Liver
Type 2 Diabetes
Published in: European Journal of Epidemiology / Issue 7/2022
Print ISSN: 0393-2990
Electronic ISSN: 1573-7284
DOI: https://doi.org/10.1007/s10654-022-00868-3

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

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