scholarly journals Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease

2021 ◽  
pp. 100437
Author(s):  
Nooshin Ghodsian ◽  
Erik Abner ◽  
Connor A. Emdin ◽  
Émilie Gobeil ◽  
Nele Taba ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Electronic Health Record ◽  
Fatty Liver Disease ◽  
Genetic Architecture ◽  
Meta Analysis ◽  
Health Record ◽  
Alcoholic Fatty Liver ◽  
Genome Wide ◽  
Alcoholic Fatty Liver Disease

scholarly journals Electronic Health Record-Based Genome-Wide Meta-Analysis and Mendelian Randomization Identify Metabolic and Phenotypic Consequences of Non-Alcoholic Fatty Liver Disease

2020 ◽  
Author(s):  
Nooshin Ghodsian ◽  
Erik Abner ◽  
Émilie Gobeil ◽  
Nele Taba ◽  
Alexis St-Amand ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Electronic Health Record ◽  
Fatty Liver Disease ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Health Record ◽  
Alcoholic Fatty Liver ◽  
Electronic Health ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) has been associated with several blood biomarkers and chronic diseases. Whether these associations underlie causal effects remains to be determined. We aimed at identifying blood metabolites, blood proteins and human diseases that are causally impacted by the presence of NAFLD using Mendelian randomization. We created a NAFLD genetic instrument from NAFLD loci (MTARC1, GCKR, LPL, TRIB1, LMO3, FTO, TM6SF2, APOE and PNPLA3) identified in a new electronic health record based-GWAS meta-analysis (6715 cases and 682,748 controls). We found a potentially causal effect of NAFLD on tyrosine metabolism as well as on blood levels of eight proteins that could potentially represent new early biomarkers of NAFLD. Using results from the UK Biobank, FinnGen and the COVID-19 Host Genetics Initiative, we found that NAFLD was not causally associated with diseases outside the spectrum of liver diseases, suggesting that the resolution of NAFLD might not prevent other diseases.

scholarly journals Electronic Health Record-Based Genome-Wide Meta-Analysis and Mendelian Randomization Identify Metabolic and Phenotypic Consequences of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Author(s):  
Nooshin Ghodsian ◽  
Erik Abner ◽  
Connor A. Emdin ◽  
Émilie Gobeil ◽  
Nele Taba ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Health Record ◽  
Susceptibility Loci ◽  
Alcoholic Fatty Liver ◽  
Genome Wide ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked with several chronic diseases. We aimed at identifying genetic variants associated with NAFLD as well as blood biomarkers that may be causally impacted by NAFLD. We performed a genome-wide meta-analysis of four cohorts of electronic health record-documented NAFLD (8434 cases and 770,180 controls) and confirmed known susceptibility loci (GCKR, MAU2/TM6SF2, APOE, and PNPLA3). We also identified potentially new loci (LPL, FTO and TR1B1) and report an effect of lower LPL expression in adipose tissue on NAFLD susceptibility. Mendelian randomization analyses identified an effect of NAFLD on tyrosine metabolism and on blood levels of three proteins. Positive genetic correlations between NAFLD and cardiometabolic traits and negative genetic correlations with parental lifespan, socio-economic factors and ketone bodies were observed. Altogether, this analysis revealed novel susceptibility loci for NAFLD and early biomarkers of NAFLD that could be used to identify patients with NAFLD.

scholarly journals Electronic Health Record-Based Genome-Wide Meta-Analysis Identifies New Susceptibility Loci for Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A501-A501
Author(s):  
Nooshin Ghodsian ◽  
Erik Abner ◽  
Émilie Gobeil ◽  
Nele Taba ◽  
Alexis St- Amand ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Human Disease ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Meta Analysis ◽  
Genetic Loci ◽  
Alcoholic Fatty Liver ◽  
Genome Wide ◽  
Alcoholic Fatty Liver Disease

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease. Observational studies documented associations of NAFLD with several chronic and infectious diseases but whether these associations underlie causal effects is unknown. The molecular mechanisms and genetic architecture of NAFLD are poorly understood. Our objectives were to identify genetic loci associated with NAFLD and determine whether the presence of NAFLD was causally associated with human diseases. Methods: We created a NAFLD genetic instrument through the identification of independent single-nucleotide polymorphisms (SNPs) associated with NAFLD in a meta-analysis of genome-wide association study (GWAS) (6715 cases and 682,748 controls). Using inverse-variance weighted Mendelian Randomization (MR), we investigated the impact of NAFLD on human disease-related phenotypes in the UK Biobank and FinnGen cohorts as well as in the COVID-19 host genetics initiative. Results: We first performed a GWAS meta-analysis of four cohorts and found variants significantly associated with NAFLD (p<5.0E-8) at six genetic loci (MTARC1, GCKR, TRIB1, LMO3, SUGP1 [TM6SF2] and PNPLA3). Using a risk factor informed Bayesian approach (bGWAS), we identify variants at three additional loci (LPL, FTO, and APOE). To determine if the association between NAFLD and human diseases shows evidence of causality, we performed MR across the human disease-related phenome (>800 diseases) using a genetic instrument for NAFLD. Results of these analyses suggest that NAFLD was not causally associated with diseases outside the spectrum of liver diseases. We also found no causal association between genetically predicted NAFLD and COVID-19-related outcomes. Conclusions: This study identified several new genetic loci associated with NAFLD. NAFLD was not causally associated with diseases outside those of the spectrum of liver diseases. This finding suggests that the resolution of NAFLD might not prevent other diseases previously associated with NAFLD.

scholarly journals FibroTest for Evaluating Fibrosis in Non-Alcoholic Fatty Liver Disease Patients: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (11) ◽  
pp. 2415
Author(s):  
Yasaman Vali ◽  
Jenny Lee ◽  
Jérôme Boursier ◽  
René Spijker ◽  
Joanne Verheij ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Advanced Fibrosis ◽  
Alcoholic Fatty Liver ◽  
Multiple Thresholds ◽  
Meta Analyses ◽  
Alcoholic Fatty Liver Disease

(1) Background: FibroTest™ is a multi-marker panel, suggested by guidelines as one of the surrogate markers with acceptable performance for detecting fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). A number of studies evaluating this test have been published after publication of the guidelines. This study aims to produce summary estimates of FibroTest™ diagnostic accuracy. (2) Methods: Five databases were searched for studies that evaluated FibroTest™ against liver biopsy as the reference standard in NAFLD patients. Two authors independently screened the references, extracted data, and assessed the quality of included studies. Meta-analyses of the accuracy in detecting different levels of fibrosis were performed using the bivariate random-effects model and the linear mixed-effects multiple thresholds model. (3) Results: From ten included studies, seven were eligible for inclusion in our meta-analysis. Five studies were included in the meta-analysis of FibroTest™ in detecting advanced fibrosis and five in significant fibrosis, resulting in an AUC of 0.77 for both target conditions. The meta-analysis of three studies resulted in an AUC of 0.69 in detecting any fibrosis, while analysis of three other studies showed higher accuracy in cirrhosis (AUC: 0.92). (4) Conclusions: Our meta-analysis showed acceptable performance (AUC > 0.80) of FibroTest™ only in detecting cirrhosis. We observed more limited performance of the test in detecting significant and advanced fibrosis in NAFLD patients. Further primary studies with high methodological quality are required to validate the reliability of the test for detecting different fibrosis levels and to compare the performance of the test in different settings.

The association between non-alcoholic fatty liver disease and atrial fibrillation: A meta-analysis

2017 ◽  
Vol 41 (5) ◽  
pp. 525-532 ◽  
Author(s):  
Karn Wijarnpreecha ◽  
Boonphiphop Boonpheng ◽  
Charat Thongprayoon ◽  
Veeravich Jaruvongvanich ◽  
Patompong Ungprasert
Keyword(s):  
Atrial Fibrillation ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Association between smoking and non-alcoholic fatty liver disease: A systematic review and meta-analysis

2018 ◽  
Vol 6 ◽  
pp. 205031211774522 ◽  
Author(s):  
Arash Akhavan Rezayat ◽  
Malihe Dadgar Moghadam ◽  
Mohammad Ghasemi Nour ◽  
Matin Shirazinia ◽  
Hamidreza Ghodsi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Liver Disease ◽  
Fatty Liver ◽  
Odds Ratio ◽  
Fatty Liver Disease ◽  
Meta Analysis ◽  
P Value ◽  
Exclusion Criteria ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background/aims: Non-alcoholic fatty liver disease is one of the most common chronic liver diseases. Some risk factors are known to influence the development of non-alcoholic fatty liver disease, but the effect of tobacco smoking on the progression of non-alcoholic fatty liver disease is controversial. The main goal of this systematic review and meta-analysis is to investigate the association between smoking and non-alcoholic fatty liver disease. Method: Electronic databases (PubMed, Scopus, and ISI Web of Science) were searched to find published articles on non-alcoholic fatty liver disease and smoking until December 2016. All relevant studies were screened by inclusion and exclusion criteria and compatible studies were chosen. The Newcastle–Ottawa Scale was used to assess the methodological quality of eligible articles. Subsequently, information was gathered based on the following: author, publication year, keywords, country, inclusion and exclusion criteria, main results, study design, conclusion, and confounder variables (age, body mass index, gender, ethnicity, and diabetes). Finally, analyses were performed using Comprehensive Meta-Analysis Software. Results: Data were extracted from 20 observational studies (9 cross-sectional, 6 case-control, 4 cohort studies, and 1 retrospective cohort study). A significant association was observed between smoking and non-alcoholic fatty liver disease with a pooled odds ratio of 1.110 (95% confidence interval, 1.028–1.199), p-value = 0.008. The statistical heterogeneity was medium with an I2 of 40.012%, p-heterogeneity = 0.074. Also there was a significant relation between non-alcoholic fatty liver disease and passive smoking with a pooled odds ratio of 1.380 (95% confidence interval, 1.199–1.588; p-value = 0.001; I2 = 59.41; p-heterogeneity = 0.117). Conclusion: Our meta-analysis demonstrated that smoking is significantly associated with non-alcoholic fatty liver disease. Further prospective studies exploring the underlying mechanisms of this association should be pursued. Also passive smoking increases the risk of non-alcoholic fatty liver disease about 1.38-fold. The effects of smoking cigarettes on active smokers (current smoker, former smoker, and total smoker) are less than passive smokers. Further studies are needed to compare the of effects of passive and active smoking on non-alcoholic fatty liver disease.

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