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Genome-wide and Men...
Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis
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- Parisinos, Constantinos A. (författare)
- Institute of Health Informatics, Faculty of Population Health Sciences, University College London, London, UK
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- Wilman, Henry R. (författare)
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, U.K. and Perspectum Diagnostics Ltd., Oxford, UK
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- Thomas, E Louise (författare)
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, U.K
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- Kelly, Matt (författare)
- Perspectum Diagnostics Ltd., Oxford, UK
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- Nicholls, Rowan C. (författare)
- Perspectum Diagnostics Ltd., Oxford, UK
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- McGonigle, John (författare)
- Perspectum Diagnostics Ltd., Oxford, UK
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- Neubauer, Stefan (författare)
- Perspectum Diagnostics Ltd., Oxford, UK. Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK
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- Hingorani, Aroon D. (författare)
- Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK
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- Patel, Riyaz S. (författare)
- Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK
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- Hemingway, Harry (författare)
- Health Data Research UK London, Institute of Health Informatics, Faculty of Population Health Sciences, University College London, London, UK
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- Bell, Jimmy D. (författare)
- Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, UK
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- Banerjee, Rajarshi (författare)
- Perspectum Diagnostics Ltd., Oxford, UK
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- Yaghootkar, Hanieh (författare)
- Luleå tekniska universitet,Omvårdnad och medicinsk teknik,Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, UK. Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, UK
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Institute of Health Informatics, Faculty of Population Health Sciences, University College London, London, UK Research Centre for Optimal Health, School of Life Sciences, University of Westminster, London, UK. and Perspectum Diagnostics Ltd., Oxford, UK (creator_code:org_t)
- Elsevier, 2020
- 2020
- Engelska.
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 73:2, s. 241-251
- Relaterad länk:
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http://www.journal-o...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- BackgroundA non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases.MethodsFirst, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures.ResultsWe identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective.ConclusionThe association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals.
Ämnesord
- TEKNIK OCH TEKNOLOGIER -- Medicinteknik -- Annan medicinteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Medical Engineering -- Other Medical Engineering (hsv//eng)
Nyckelord
- Magnetic resonance imaging
- cT1
- fibrosis
- steatohepatitis
- metabolic syndrome
- genome-wide association study
- Medical Engineering
- Medicinsk teknik
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Parisinos, Const ...
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Wilman, Henry R.
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Thomas, E Louise
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Kelly, Matt
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Nicholls, Rowan ...
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McGonigle, John
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visa fler...
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Neubauer, Stefan
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Hingorani, Aroon ...
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Patel, Riyaz S.
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Hemingway, Harry
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Bell, Jimmy D.
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Banerjee, Rajars ...
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Yaghootkar, Hani ...
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visa färre...
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