0000000000243948

AUTHOR

Mark S. Silverberg

showing 4 related works from this author

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

2018

ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportiona…

Male0301 basic medicineOncologyCandidate geneCholangitismedicine.medical_treatmentMedizinTrasplantament hepàticGenome-wide association studyKaplan-Meier EstimateLIVER FIBROSISLiver transplantationBioinformaticsSclerosingOral and gastrointestinalPrimary sclerosing cholangitis; genetics; liver transplantationCohort StudiesACTIVATION0302 clinical medicineMED/12 - GASTROENTEROLOGIAMULTIPLE2.1 Biological and endogenous factorsEPIDEMIOLOGYgeneticsAetiologyCIRRHOSISliver transplantationBilious diseases and biliousnessPrimary sclerosing cholangitisLiver Diseasedigestive oral and skin physiologyGastroenterologySingle NucleotidePrimary sclerosing cholangitiMiddle Aged3. Good healthULCERATIVE-COLITISDisease ProgressionFemale030211 gastroenterology & hepatologyAdultmedicine.medical_specialtyCholangitis SclerosingChronic Liver Disease and CirrhosisClinical SciencesMalalties del tracte biliarSingle-nucleotide polymorphismHEPATIC STELLATE CELLSPolymorphism Single NucleotideInternational PSC Study GroupArticlePrimary sclerosing cholangitisPaediatrics and Reproductive Medicine03 medical and health sciencesRare DiseasesClinical ResearchInternal medicineGeneticsmedicineHumansPolymorphismGENOME-WIDE ASSOCIATIONAlleleDigestive Diseases - (Gallbladder)Survival analysisProportional Hazards ModelsMALIGNANCYThe UK PSC ConsortiumTransplantationGastroenterology & Hepatologybusiness.industryProportional hazards modelmedicine.diseaseRISK LOCILogistic Models030104 developmental biology3121 General medicine internal medicine and other clinical medicinegeneticHepatic transplantationThrombospondinsDigestive DiseasesbusinessGenèticaGut
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Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis

2013

To access publisher's full text version of this article click on the hyperlink at the bottom of the page Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci sh…

Linkage disequilibriumHISTONE DEACETYLASEGenotyping Techniquesendocrine system diseasesGenome-wide association studyDiseaseBioinformaticsLinkage Disequilibrium0302 clinical medicineGene FrequencyRisk FactorsOligonucleotide Array Sequence Analysis0303 health sciencesCrohn's diseaseeducation.field_of_studydigestive oral and skin physiologyCELIAC-DISEASEGenetic PleiotropyLifrarsjúkdómar3. Good healthFALSE DISCOVERY RATEULCERATIVE-COLITISgenetic association studydisease genetics030211 gastroenterology & hepatologySUSCEPTIBILITY LOCIPopulationCholangitis SclerosingSingle-nucleotide polymorphismHuman leukocyte antigenGENETIC RISKBiologyliverPolymorphism Single Nucleotidedigestive systemArticlePrimary sclerosing cholangitis03 medical and health sciencesFUNCTIONAL SIMILARITYGeneticsmedicineHumansGENOME-WIDE ASSOCIATIONeducation030304 developmental biologyNATURAL-HISTORYArfgengimedicine.diseasedigestive system diseasesimmunogeneticsGenetic LociCase-Control StudiesImmunologyGenome-Wide Association StudyINFLAMMATORY-BOWEL-DISEASE
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Brief Report: Functional Interaction of Endoplasmic Reticulum Aminopeptidase 2 and HLA-B27 Activates the Unfolded Protein Response.

2017

Objective: The basic mechanisms underlying the pathogenesis of ankylosing spondylitis (AS) remain unresolved. We previously reported an association of the single-nucleotide polymorphism (SNP) rs2549782 in the endoplasmic reticulum aminopeptidase 2 gene (ERAP2) with AS. It is known that patients homozygous for the G allele (GG) of another ERAP2 SNP, rs2248374, lack expression of ERAP2 (ERAP2 null). The present study utilized this information to study the impact of ERAP2 deficiency on HLA–B27 expression in patients with AS, specifically focusing on the functional interaction of ERAP2 and HLA–B27 in peripheral blood mononuclear cells (PBMCs) from patients with AS and assessing the effects …

0301 basic medicineMaleX-Box Binding Protein 1Aminopeptidases0302 clinical medicineImmunology and AllergyRNA Small InterferingEndoplasmic Reticulum Chaperone BiPHLA-B27 AntigenHeat-Shock ProteinsAlleleBlottingReverse Transcriptase Polymerase Chain ReactionHeat-Shock ProteinSingle NucleotideMiddle AgedFlow CytometryCCAAT-Enhancer-Binding Protein3. Good healthUp-RegulationFemaleWesternHumanAnkylosingAdultAminopeptidaseMononuclearImmunologyBlotting WesternSingle-nucleotide polymorphismBiologyMajor histocompatibility complexSmall InterferingPolymorphism Single NucleotideAdult; Alleles; Aminopeptidases; Blotting Western; CCAAT-Enhancer-Binding Proteins; Cell Line; Female; Flow Cytometry; HLA-B27 Antigen; Heat-Shock Proteins; Humans; Leukocytes Mononuclear; Male; Middle Aged; Polymorphism Single Nucleotide; RNA Small Interfering; Reverse Transcriptase Polymerase Chain Reaction; Spondylitis Ankylosing; Unfolded Protein Response; Up-Regulation; X-Box Binding Protein 1; Immunology and Allergy; Rheumatology; ImmunologyCell Line03 medical and health sciencesDownregulation and upregulationRheumatologyHumansSpondylitis AnkylosingAllelePolymorphismAlleles030203 arthritis & rheumatologySpondylitiHLA-B27LeukocyteEndoplasmic reticulum aminopeptidase 2X-Box Binding Protein 1Molecular biologySettore MED/16 - Reumatologia030104 developmental biologyUnfolded protein responsebiology.proteinCCAAT-Enhancer-Binding ProteinsLeukocytes MononuclearUnfolded Protein ResponseRNAArthritisrheumatology (Hoboken, N.J.)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

2010

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 x 10(-8)). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with gen…

Candidate geneGenetic LinkagePROTEINGenome-wide association studyInflammatory bowel diseaseGenomeACTIVATION0302 clinical medicineCrohn DiseaseSEQUENCE VARIANTSGenetics0303 health sciencesGenomeNEDD4 FAMILYCOMMON VARIANTSASSOCIATION3. Good health030220 oncology & carcinogenesis10076 Center for Integrative Human PhysiologyComputational Biology; Crohn Disease; Genetic Linkage; Genetic Loci; Genetic Variation; Genome Human; Humans; Reproducibility of Results; Genetic Predisposition to Disease; Genome-Wide Association Study; Geneticsinflammatory-bowel-disease sequence variants common variants nedd4 family association gene identification receptor protein activationHuman/dk/atira/pure/subjectarea/asjc/1300/1311Locus (genetics)610 Medicine & healthBiology03 medical and health sciences1311 GeneticsGenetic linkagemedicineGeneticsHumansGenetic Predisposition to Disease030304 developmental biologyGenetic associationIDENTIFICATIONRECEPTORComputational BiologyGenetic VariationReproducibility of Resultsmedicine.diseaseGENESettore MED/03 - Genetica Medica10199 Clinic for Clinical Pharmacology and ToxicologyGenetic Loci570 Life sciences; biologyHuman genomegenome-wide scan.meta-analysis.crohn's diseaseGenome-Wide Association StudyINFLAMMATORY-BOWEL-DISEASE
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