Title | Estimating the Effect of Liver and Pancreas Volume and Fat Content on Risk of Diabetes: A Mendelian Randomization Study |
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Type | Journal article |
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Authors | Martin, Susan, Sorokin, Elena P, Thomas, E Louise, Sattar, Naveed, Cule, Madeleine, Bell, Jimmy D and Yaghootkar, H. |
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Abstract | 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. 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. 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. 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 2 diabetes. [Abstract copyright: © 2022 by the American Diabetes Association.] |
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Keywords | Liver fat |
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| Pancreas fat |
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| Pancreas volume |
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| MRI scan |
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| Type 1 diabetes |
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| Type 2 diabetes |
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| Mendelian randomization |
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Journal | Diabetes Care |
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Journal citation | 45 (2), pp. 460-468 |
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ISSN | 1935-5548 |
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Year | 2022 |
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Publisher | American Diabetes Association |
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Accepted author manuscript | File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.2337/dc21-1262 |
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PubMed ID | 34983059 |
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Web address (URL) | https://diabetesjournals.org/care/article/doi/10.2337/dc21-1262/139118/Estimating-the-Effect-of-Liver-and-Pancreas-Volume |
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Publication dates |
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Published | 17 Jan 2022 |
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Published online | 22 Dec 2021 |
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Supplemental file | File Access Level Open (open metadata and files) |
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