دورية أكاديمية
Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation.
| العنوان: | Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation. |
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| المؤلفون: | Martin, S, Tyrrell, J, Thomas, EL, Bown, MJ, Wood, AR, Beaumont, RN, Tsoi, LC, Stuart, PE, Elder, JT, Law, P, Houlston, R, Kabrhel, C, Papadimitriou, N, Gunter, MJ, Bull, CJ, Bell, JA, Vincent, EE, Sattar, N, Dunlop, MG, Tomlinson, IPM, Lindström, S, INVENT consortium, Bell, JD, Frayling, TM, Yaghootkar, H |
| المساهمون: | Law, Philip, Houlston, Richard |
| بيانات النشر: | eLIFE SCIENCES PUBL LTD |
| سنة النشر: | 2022 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Mendelian randomisation, cancer, cardiovascular disease, epidemiology, favourable adiposity, genetics, genomics, global health, human, obesity, Adiposity, Adult, Aged, 80 and over, Body Mass Index, Cardiometabolic Risk Factors, Female, Genome-Wide Association Study, Humans, Male, Mendelian Randomization Analysis, Middle Aged |
| جغرافية الموضوع: | England |
| الوصف: | BACKGROUND: Some individuals living with obesity may be relatively metabolically healthy, whilst others suffer from multiple conditions that may be linked to adverse metabolic effects or other factors. The extent to which the adverse metabolic component of obesity contributes to disease compared to the non-metabolic components is often uncertain. We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases. METHODS: We selected 37 chronic diseases associated with obesity and genetic variants associated with different aspects of excess weight. These genetic variants included those associated with metabolically 'favourable adiposity' (FA) and 'unfavourable adiposity' (UFA) that are both associated with higher adiposity but with opposite effects on metabolic risk. We used these variants and two sample MR to test the effects on the chronic diseases. RESULTS: MR identified two sets of diseases. First, 11 conditions where the metabolic effect of higher adiposity is the likely primary cause of the disease. Here, MR with the FA and UFA genetics showed opposing effects on risk of disease: coronary artery disease, peripheral artery disease, hypertension, stroke, type 2 diabetes, polycystic ovary syndrome, heart failure, atrial fibrillation, chronic kidney disease, renal cancer, and gout. Second, 9 conditions where the non-metabolic effects of excess weight (e.g. mechanical effect) are likely a cause. Here, MR with the FA genetics, despite leading to lower metabolic risk, and MR with the UFA genetics, both indicated higher disease risk: osteoarthritis, rheumatoid arthritis, osteoporosis, gastro-oesophageal reflux disease, gallstones, adult-onset asthma, psoriasis, deep vein thrombosis, and venous thromboembolism. CONCLUSIONS: Our results assist in understanding the consequences of higher adiposity uncoupled from its adverse metabolic effects, including the risks to individuals with high body mass ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Electronic; application/pdf |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | ARTN e72452; 72452; eLife, 2022, 11 pp. e72452 -; https://repository.icr.ac.uk/handle/internal/5409Test |
| DOI: | 10.7554/eLife.72452 |
| الإتاحة: | https://doi.org/10.7554/eLife.72452Test https://repository.icr.ac.uk/handle/internal/5409Test |
| حقوق: | http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.45F3DE47 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.72452 |