0000000001132789

AUTHOR

Katherine A. Siminovitch

showing 4 related works from this author

Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.

2010

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

Liver CirrhosisOncologyCanadamedicine.medical_specialtyCirrhosisEuropean Continental Ancestry GroupLOCIPRIMARY BILIARY CIRRHOSIS; GENOME WIDE ASSOCIATION; LOCIGenome-wide association studyLocus (genetics)genetics Genome Genome-Wide Association Study Humans Interferon Regulatory Factors Liver CirrhosiBiologyBiliary Meta-Analysis as Topic Odds RatioWhite PeopleArticleGENOME WIDE ASSOCIATIONAlleles Canada European Continental Ancestry Groupprimary biliary cirrhosiPrimary biliary cirrhosisMeta-Analysis as TopicMED/12 - GASTROENTEROLOGIAIL12AInternal medicineOdds RatioGeneticsmedicineHumansAllelegenomeAlleles Canada European Continental Ancestry Group; genetics Genome Genome-Wide Association Study Humans Interferon Regulatory Factors Liver Cirrhosis; Biliary Meta-Analysis as Topic Odds RatioAllelesprimary biliary cirrhosis genome-wide meta-analysesGeneticsLiver Cirrhosis BiliaryBiliaryOdds ratiomedicine.diseasePrimary biliary cirrhosisInterferon Regulatory FactorsCohortGenome-Wide Association Study
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X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

2021

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…

Canadian-US PBC Consortium0301 basic medicineMaleLinkage disequilibriumGenome-wide association studyDiseasePBCSettore MED/03 - GENETICA MEDICALinkage Disequilibrium0302 clinical medicineUK-PBC ConsortiumGenotypeMitochondrial Precursor Protein Import Complex ProteinsItalian PBC Genetics Study GroupOdds RatioX-Wide Association StudyJapan PBC-GWAS ConsortiumX chromosomeGeneticsLiver Cirrhosis BiliaryGastroenterologyForkhead Transcription FactorsDNA-Binding ProteinsShal Potassium Channels030211 gastroenterology & hepatologyFemaleAdultMonosaccharide Transport ProteinsSuperenhancerLocus (genetics)Single-nucleotide polymorphismBiologyProtein Serine-Threonine KinasesPolymorphism Single NucleotideArticleWhite People03 medical and health sciencesAsian PeopleProto-Oncogene ProteinsEndopeptidasesHumansCell LineageGenetic Predisposition to DiseaseMeta-analysiGenetic associationChromosomes Human XGastroenterology & HepatologyHepatology1103 Clinical SciencesMeta-analysis030104 developmental biologyGenetic Loci1114 Paediatrics and Reproductive MedicineMeta-analysis; Superenhancer; X-Wide Association Study1109 NeurosciencesCarrier ProteinsGenome-Wide Association Study
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An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

2021

[BACKGROUND & AIMS] Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intra-hepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. [METHODS] We combined new and existing genotype data for 10, 516 cases and 20, 77…

Liver CirrhosisALSPAC; ERN RARE-LIVER; Genomic co-localization; Network-based in silico drug efficacy screening; UK-PBC0301 basic medicineCandidate geneALSPAC; ERN RARE-LIVER; Genomic co-localization; Network-based in silico drug efficacy screening; UK-PBC; Genome-Wide Association Study; Humans; Liver Cirrhosis BiliaryItalian PBC Study GroupLD SCORE REGRESSIONJapan-PBC-GWAS ConsortiumGenome-wide association studyLocus (genetics)DiseaseSUSCEPTIBILITYPBCChronic liver diseaseBioinformaticsGENETIC ASSOCIATION1117 Public Health and Health Services03 medical and health sciences0302 clinical medicineUK-PBC ConsortiumGenotypeHumansMedicineNetwork-based in silico drug efficacy screeningGenetic associationScience & TechnologyGastroenterology & HepatologyHepatologyLiver Cirrhosis Biliarybusiness.industryBiliaryChinese PBC Consortium1103 Clinical SciencesALSPACmedicine.diseasePBC Consortia030104 developmental biologyMeta-analysisERN RARE LIVER030211 gastroenterology & hepatologyGenomic co-localizationUK-PBCUS PBC ConsortiumERN RARE-LIVERCanadian PBC ConsortiumbusinessLife Sciences & BiomedicineGenome-Wide Association StudyHuman
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International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

2015

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.

Liver CirrhosisGenetics and Molecular Biology (all)pathogenesirisk assessment EMTREE medical terms: Articlegenetic associationgenotypeEMTREE drug terms: chemokine receptor CCR6genetic riskBiochemistrymeta-analysiprimary biliary cirrhosichemokine receptor CCR6 [EMTREE drug terms]single nucleotide polymorphismgenetic variabilityArticle [risk assessment EMTREE medical terms]Liver Cirrhosis BiliarypathogenesisBiliaryChemistry (all)STAT protein GEOBASE Subject Index: disease treatmentcohort analysisgenome wide meta analysis PBCsignal transductiongene locuscohort analysiCBPArticle*Physics and Astronomy (all)macrophage inflammatory protein 3alphaHumanscontrolled studyhumaninterleukin 27genomeBiochemistry Genetics and Molecular Biology (all)meta analysiinterleukin 12p40EMTREE drug terms: chemokine receptor CCR6; interleukin 12; interleukin 12p40; interleukin 27; Janus kinase; macrophage inflammatory protein 3alpha; STAT protein GEOBASE Subject Index: disease treatment; genome; meta-analysis; pathogen; risk assessment EMTREE medical terms: Article; cohort analysis; controlled study; gene locus; genetic association; genetic predisposition; genetic risk; genetic variability; genotype; human; major clinical study; meta analysis; pathogenesis; primary biliary cirrhosis; signal transduction; single nucleotide polymorphismmajor clinical studyprimary biliary cirrhosismeta-analysisdisease treatment [STAT protein GEOBASE Subject Index]Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)Humans; Liver Cirrhosis; Biliary; Genome-Wide Association Study; Biochemistry; Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)gene locuinterleukin 12genetic predispositionJanus kinasepathogenmeta analysisHumans; Liver Cirrhosis Biliary; Genome-Wide Association Study; Biochemistry Genetics and Molecular Biology (all); Chemistry (all); Physics and Astronomy (all)Genome-Wide Association Study
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