| Title: | Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study. |
| Journal: | Diabetes Care |
| Published: | 17 Jan 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34983059/ |
| DOI: | https://doi.org/10.2337/dc21-1262 |
| URL: | https://diabetesjournals.org/care/article-pdf/45/2/460/642565/dc211262.pdf |
| Citations: | 37 (28 in last 2 years) as of 8 Aug 2024 |
Publication 12602
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Abstract
OBJECTIVE: Fat content and volume of liver and pancreas are associated with risk of diabetes in observational studies; whether these associations are causal is unknown. We conducted a Mendelian randomization (MR) study to examine causality of such associations.</p>
RESEARCH DESIGN AND METHODS: We used genetic variants associated (P < 5 × 10-8) with the exposures (liver and pancreas volume and fat content) using MRI scans of UK Biobank participants (n = 32,859). We obtained summary-level data for risk of type 1 (9,358 cases) and type 2 (55,005 cases) diabetes from the largest available genome-wide association studies. We performed inverse-variance weighted MR as main analysis and several sensitivity analyses to assess pleiotropy and to exclude variants with potential pleiotropic effects.</p>
RESULTS: Observationally, liver fat and volume were associated with type 2 diabetes (odds ratio per 1 SD higher exposure 2.16 [2.02, 2.31] and 2.11 [1.96, 2.27], respectively). Pancreatic fat was associated with type 2 diabetes (1.42 [1.34, 1.51]) but not type 1 diabetes, and pancreas volume was negatively associated with type 1 diabetes (0.42 [0.36, 0.48]) and type 2 diabetes (0.73 [0.68, 0.78]). MR analysis provided evidence only for a causal role of liver fat and pancreas volume in risk of type 2 diabetes (1.27 [1.08, 1.49] or 27% increased risk and 0.76 [0.62, 0.94] or 24% decreased risk per 1SD, respectively) and no causal associations with type 1 diabetes.</p>
CONCLUSIONS: Our findings assist in understanding the causal role of ectopic fat in the liver and pancreas and of organ volume in the pathophysiology of type 1 and type 2 diabetes.</p>
8 Keywords
- Diabetes Mellitus, Type 2
- Genome-Wide Association Study
- Humans
- Liver
- Mendelian Randomization Analysis
- Pancreas
- Polymorphism, Single Nucleotide
- Risk Factors
7 Authors
- Susan Martin
- Elena P Sorokin
- E Louise Thomas
- Naveed Sattar
- Madeleine Cule
- Jimmy D Bell
- Hanieh Yaghootkar
1 Application
| Application ID | Title |
|---|---|
| 44584 | Enriched Image Based Phenotypes for Health Exploration and Discovery |
Enabling scientific discoveries that improve human health