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

Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni Li Eline H.van den Berg alexander kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.Lopera-Maya Alexandra Zhernakova Lifelines Cohort Study Vincent E.de Meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China Laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** 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 *** 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 *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFLD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

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