Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.

How to select the quantitative magnetic resonance technique for subjects with fatty liver:A systematic review

BACKGROUND Early quantitative assessment of liver fat content is essential for patients with fatty liver disease.Mounting evidence has shown that magnetic resonance(MR)technique has high accuracy in the quantitative analysis of fatty liver,and is suitable for monitoring the therapeutic effect on fatty liver.However,many packaging methods and postprocessing functions have puzzled radiologists in clinical applications.Therefore,selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging.AIM To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver.METHODS We completed a systematic literature review of quantitative MR techniques for detecting fatty liver,following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol.Studies were retrieved from PubMed,Embase,and Cochrane Library databases,and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria.The Reference Citation Analysis database(https://www.referencecitationanalysis.com)was used to analyze citation of articles which were included in this review.RESULTS Forty studies were included for spectroscopy,two-point Dixon imaging,and multiple-point Dixon imaging comparing liver biopsy to other imaging methods.The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed.CONCLUSION The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression.