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Epidemiology and Population Health

Genetically predicted visceral adipose tissue and risk of nine non-tumour gastrointestinal diseases: evidence from a Mendelian randomization study

Abstract

Background

Numerous studies have linked visceral adipose tissue (VAT) to gastrointestinal diseases. However, it remains unclear whether these associations reflect causal relationships.

Methods

We used a two-sample Mendelian randomization (MR) approach to elucidate the causal effect of VAT on nine non-tumour gastrointestinal diseases. The inverse-variance weighted method was used to perform the MR analyses. Complementary and multivariable MR analyses were performed to confirm the results.

Results

Genetically predicted higher VAT was associated with an increased risk of gastro-oesophageal reflux disease (GORD) (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09–1.34; P = 3.06 × 10−4), duodenal ulcer (DU) (OR, 1.40; 95% CI, 1.10–1.77; P = 0.005), cholelithiasis (OR, 1.75; 95% CI, 1.53–2.00; P = 1.14 × 10−16), and non-alcoholic fatty liver disease (NAFLD) (OR, 2.68; 95% CI, 1.87–3.82; P = 6.26 × 10−8). There were suggestive associations between VAT and gastric ulcer (GU) (OR, 1.22; 95% CI, 1.01–1.48; P = 0.035) and acute pancreatitis (AP) (OR, 1.26; 95% CI, 1.05–1.52; P = 0.013). However, there was little evidence to support the associations between VAT and inflammatory bowel disease, irritable bowel syndrome, or chronic pancreatitis. The associations with GORD, GU, and NAFLD remained in the multivariable MR analyses with adjustment for body mass index (BMI).

Conclusions

This study provided evidence in support of causal associations between VAT and GORD, GU, DU, cholelithiasis, AP, and NAFLD. Moreover, the associations between GORD, GU, and NAFLD were independent of the effect of BMI.

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Fig. 1: Schematic representation of the study design and main results of this Mendelian randomization (MR) study of the associations between visceral adipose tissue and nine non-tumour gastrointestinal diseases.
Fig. 2: Mendelian randomization associations of visceral adipose tissue with nine non-tumour gastrointestinal diseases.
Fig. 3: Multivariable Mendelian randomization associations of visceral adipose tissue with nine non-tumour gastrointestinal diseases adjusting for body mass index.

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Data availability

The data used in this study were publicly available and can be accessed via the links described in the supplementary material. The R-code used for this study is available from the corresponding author on reasonable request.

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Acknowledgements

We want to acknowledge all the participants and investigators of the GWAS involved in the present study for generously sharing the summary-level data.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81873484).

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All authors contributed to the study conception and design. Material preparation, data collection and analyses were performed by Xingang Sun and Yifan Yuan. The first draft of the manuscript was written by Xingang Sun, Yifan Yuan, and Lu Chen. Liangrong Zheng and Mei Ye reviewed the final manuscript. All authors read and approved the final manuscript.

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Correspondence to Mei Ye or Liangrong Zheng.

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Sun, X., Yuan, Y., Chen, L. et al. Genetically predicted visceral adipose tissue and risk of nine non-tumour gastrointestinal diseases: evidence from a Mendelian randomization study. Int J Obes 47, 406–412 (2023). https://doi.org/10.1038/s41366-023-01279-4

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