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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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Pharmacomicrobiomics： a novel route towards personalized medicine？

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Protein & Cell 2018年第5期9卷 432-445页

作者： Marwah Doestzada Arnau Vich Vila alexandra zhernakova Debby P.Y. Koonen Rinse K. Weersma Daan J. TOUW Folkert Kuipers Cisca Wijmenga Jingyuan Fu Departments of Genetics University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Paediatrics University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Gastroenterology & Hepatology University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Clinical Pharmacy & Pharmacology University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Laboratory Medicine University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands K.G. Jebsen Coeliac Disease Research Centre Department of Immunology University of Oslo P.O. Box 1072 Blindern 0316 Oslo Norway

Inter-individual heterogeneity in drug response is a serious problem that affects the patient＇s wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recog- nized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition. Pharmacomicrobiomics is an emerging field that investigates the interplay of microbiome variation and drugs response and disposi- tion （absorption, distribution, metabolism and excretion）. In this review, we provide a historical overview and examine current state-of-the-art knowledge on the complex interactions between gut microbiome, host and drugs. We argue that combining pharmacogenomics and pharmacomicrobiomics will provide an important foundation for making major advances in personalized medicine.

关键词： gut microbiome drug metabolism personalized medicine

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