6533b7dafe1ef96bd126e3f3

RESEARCH PRODUCT

Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis

Carl A. AndersonKonstantinos N. LazaridisIsabelle CleynenIsabelle CleynenWesley K. ThompsonO. A. AndreassenOle A. AndreassenAndreas TeufelFelix BraunEinar BjörnssonJohn D. RiouxJohn D. RiouxRoger W. ChapmanInke R. KönigJavier Gutierrez-achuryGabriele MayrStefan SchreiberStephan BrandMitja MitrovicAnnika BergquistMichael P. MannsJean-paul AchkarJean-paul AchkarSimon M. RushbrookCyriel Y. PonsioenMartina SterneckKirsten Muri BobergKirsten Muri BobergChristian RustAndrew J. SchorkAlbert ParésGideon M. HirschfieldGideon M. HirschfieldGraeme J.m. AlexanderEspen MelumEspen MelumBertus EksteenJuliane WinkelmannCisca WijmengaIngo ThomsenHanns-ulrich MarschallIsis Ricaño-ponceErik SchrumpfErik SchrumpfPeter J. P. CroucherJimmy Z. LiuRichard H. DuerrNadezhda Tsankova DonchevaAnnarosa FloreaniEva EllinghausMarkus M. NöthenBrian D. JuranJudy H. ChoMario AlbrechtStefan HermsTobias J. WeismüllerLeonid PadyukovVirpi LeppaMorten H. VatnMorten H. VatnMorten H. VatnMark S. SilverbergTobias MüllerOlivier ChazouillèresDomenico AlvaroChristoph SchrammRuslan DorfmanRichard SandfordDavid A. Van HeelRinse K. WeersmaSuna Onengut-gumuscuAnders M. DaleMartti FärkkiläBrijesh SrivastavaSeverine VermeireTrine FolseraasTrine FolseraasVito AnnesePietro InvernizziTejas ShahDaniel GotthardtJanna SaarelaChristopher L. BowlusSigrid NæssSigrid NæssAndrew MasonStephen S. RichJohannes R. HovPeter R. DurieAndre FrankeKristian HveemTom H. KarlsenPiotr MilkiewiczMiquel SansGeorgios N. DalekosDavid Ellinghaus

subject

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

description

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 showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases. Norwegian PSC Research Center German Ministry of Education and Research through the National Genome Research Network 01GS0809-GP7 Deutsche Forschungsgemeinschaft FR 2821/2-1 Integrated Research and Treatment Center-Transplantation 01EO0802 PopGen Biobank Wellcome Trust 098051 info:eu-repo/grantAgreement/EC/FP7/262055

yearjournalcountryeditionlanguage
2013-06-01
http://www.escholarship.org/uc/item/3dv430kz