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Article
Benoit Arsenault
Department of Medicine, Laval University, Quebec
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
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.
Keywords
Electronic Health Record, Non alcoholic Fatty Liver Disease, Mendelian randomization blood biomarkers and chronic diseases
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- SupplTablesNAFLDreverseMRpaperBA20210304.xlsx
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- FiguresNAFLDMRpaperNG20210304.pptx
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This is a preprint. It has not completed peer review.
Article
Benoit Arsenault
Department of Medicine, Laval University, Quebec
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 26 Mar, 2021
No community comments so far
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Medical Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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