Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

MRI-based corrected T1 (cT1) is a non-invasive method to grade the severity of steatohepatitis and liver fibrosis. 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...

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Bibliographic Details
Published in:Journal of hepatology 2020-08, Vol.73 (2), p.241-251
Main Authors: Parisinos, Constantinos A., Wilman, Henry R., Thomas, E. Louise, Kelly, Matt, Nicholls, Rowan C., McGonigle, John, Neubauer, Stefan, Hingorani, Aroon D., Patel, Riyaz S., Hemingway, Harry, Bell, Jimmy D., Banerjee, Rajarshi, Yaghootkar, Hanieh
Format: Article
Language:English
Subjects:
Adipose tissue
Biobanks
Body mass index
Cation Transport Proteins - genetics
Cell injury
cT1
Diabetes mellitus (non-insulin dependent)
Disease
Europe - epidemiology
Fatty liver
Fatty Liver - epidemiology
Fatty Liver - genetics
Female
Fibrosis
Genetic diversity
Genetic Predisposition to Disease
Genetic Variation
Genome-wide association studies
Genome-Wide Association Study
Genomes
Hepatocytes
Humans
Inflammation
Insulin
Liver
Liver - diagnostic imaging
Liver - pathology
Liver Cirrhosis - epidemiology
Liver Cirrhosis - genetics
Liver diseases
Magnetic resonance imaging
Magnetic Resonance Imaging - methods
Male
Medical Engineering
Medicinsk teknik
Mendelian Randomization Analysis
Metabolic syndrome
Metabolic Syndrome - epidemiology
Metabolic Syndrome - genetics
Metabolism
Metal ions
Middle Aged
Polymorphism, Single Nucleotide
Protective Factors
Risk Assessment - methods
Steatohepatitis
Transaminases
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Summary:MRI-based corrected T1 (cT1) is a non-invasive method to grade the severity of steatohepatitis and liver fibrosis. 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. First, we performed a genome-wide association study (GWAS) in 14,440 Europeans, with liver cT1 measures, from the UK Biobank. 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. We identified 6 independent genetic variants associated with liver cT1 that reached the GWAS significance threshold (p 
ISSN:0168-8278
1600-0641
1600-0641
DOI:10.1016/j.jhep.2020.03.032