0000000000605953

AUTHOR

Jon K. Laerdahl

showing 3 related works from this author

Mutational Characterization of the Bile Acid Receptor TGR5 in Primary Sclerosing Cholangitis

2010

Background: TGR5, the G protein-coupled bile acid receptor 1 (GPBAR1), has been linked to inflammatory pathways as well as bile homeostasis, and could therefore be involved in primary sclerosing cholangitis (PSC) a chronic inflammatory bile duct disease. We aimed to extensively investigate TGR5 sequence variation in PSC, as well as functionally characterize detected variants.Methodology/Principal Findings: Complete resequencing of TGR5 was performed in 267 PSC patients and 274 healthy controls. Six nonsynonymous mutations were identified in addition to 16 other novel single-nucleotide polymorphisms. To investigate the impact from the nonsynonymous variants on TGR5, we created a receptor mod…

Nonsynonymous substitutionMaleModels MolecularCandidate geneLinkage disequilibriumProtein ConformationDNA Mutational Analysislcsh:MedicineGenome-wide association studySUSCEPTIBILITYMULTIPLE SEQUENCE ALIGNMENTSReceptors G-Protein-CoupledMice0302 clinical medicineChildlcsh:ScienceGenetics and Genomics/Genetics of DiseaseGENE-EXPRESSIONGenetics0303 health sciencesMultidisciplinaryGastroenterology and Hepatology/Biliary TractCROHN-DISEASEMiddle AgedG protein-coupled bile acid receptor3. Good healthGenetics and Genomics/Gene FunctionULCERATIVE-COLITISChromosomes Human Pair 2WEB SERVER030211 gastroenterology & hepatologyFemaleResearch ArticleAdultAdolescentCholangitis SclerosingSingle-nucleotide polymorphismLocus (genetics)BiologyGenetics and Genomics/Complex TraitsPrimary sclerosing cholangitis03 medical and health sciencesYoung AdultDogsPROTEIN-COUPLED RECEPTORSLIVER-DISEASEmedicineAnimalsHumansAmino Acid SequenceBOWEL-DISEASE030304 developmental biologyAgedGastroenterology and Hepatology/Inflammatory Bowel DiseaseCYSTIC-FIBROSISlcsh:Rmedicine.diseaseGene Expression RegulationMutationCancer researchCattleColitis Ulcerativelcsh:Q
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Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci

2012

Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS). Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing. Results: Seventeen SNPs representing 1…

MaleLinkage disequilibriumendocrine system diseasesGenome-wide association studyPrimary biliary cirrhosisGenotypeBLOOD-GROUPBileChildPOPULATIONAged 80 and overGeneticseducation.field_of_studyPrimary sclerosing cholangitisdigestive oral and skin physiologyMiddle AgedFucosyltransferasesChild PreschoolDISEASESFemaleNeprilysinReceptors Tumor Necrosis Factor Member 14B-LYMPHOCYTEAdultRiskGenome-wide association studyAdolescentGenotypeSUSCEPTIBILITY LOCIFUT2Cholangitis SclerosingPopulationT-LYMPHOCYTE ATTENUATORSingle-nucleotide polymorphismBiologyPolymorphism Single Nucleotidedigestive systemArticlePrimary sclerosing cholangitisGenetic predispositionmedicineImmunogeneticsHumansGenetic Predisposition to DiseaseeducationMETAANALYSISAgedNON-SECRETOR STATUSHepatologymedicine.diseaseGENEdigestive system diseasesSingle nucleotide polymorphismGenetic LociImmunology
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Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci

2011

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 x 10(-16) and P = 4.1 x 10(-8), respectively).

Cholangitis SclerosingPATHOGENESISSingle-nucleotide polymorphismGenome-wide association studyHuman leukocyte antigenBiologyInflammatory bowel diseasePolymorphism Single Nucleotidedigestive systemArticlePrimary sclerosing cholangitisPathogenesisCohort StudiesHLA AntigensProto-Oncogene ProteinsGeneticsmedicineHumansGenetic Predisposition to DiseaseBOWEL-DISEASEGenetic associationBcl-2-Like Protein 11Bile ductHepatocyte Growth FactorGene Expression Profilingdigestive oral and skin physiologyMembrane Proteinsmedicine.diseasedigestive system diseasesmedicine.anatomical_structureGenetic LociImmunologyApoptosis Regulatory ProteinsGenome-Wide Association Study
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