Abstract
Abstract
Background
Observational studies have linked adiposity and especially abdominal adiposity to liver fat accumulation and non-alcoholic fatty liver disease. These traits are also associated with type 2 diabetes and coronary artery disease but the causal factor(s) underlying these associations remain unexplored.
Methods
We used a multivariable Mendelian randomization study design to determine whether body mass index and waist circumference were causally associated with non-alcoholic fatty liver disease using publicly available genome-wide association study summary statistics of the UK Biobank (n = 461,460) and of non-alcoholic fatty liver disease (8434 cases and 770,180 control). A multivariable Mendelian randomization study design was also used to determine the respective causal contributions of waist circumference and liver fat (n = 32,858) to type 2 diabetes and coronary artery disease.
Results
Using multivariable Mendelian randomization we show that waist circumference increase non-alcoholic fatty liver disease risk even when accounting for body mass index (odd ratio per 1-standard deviation increase = 2.35 95% CI = 1.31–4.22, p = 4.2e−03), but body mass index does not increase non-alcoholic fatty liver disease risk when accounting for waist circumference (0.86 95% CI = 0.54–1.38, p = 5.4e−01). In multivariable Mendelian randomization analyses accounting for liver fat, waist circumference remains strongly associated with both type 2 diabetes (3.27 95% CI = 2.89–3.69, p = 3.8e−80) and coronary artery disease (1.66 95% CI = 1.54–1.8, p = 3.4e−37).
Conclusions
These results identify waist circumference as a strong, independent, and causal contributor to non-alcoholic fatty liver disease, type 2 diabetes and coronary artery disease, thereby highlighting the importance of assessing body fat distribution for the prediction and prevention of cardiometabolic diseases.
Funder
EC | European Regional Development Fund
Publisher
Springer Science and Business Media LLC
Cited by
7 articles.
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