biostudies-literatureAsselta RMinistero della SaluteNational Natural Science Foundation of China-Yunnan Joint FundNIDDK NIH HHSMedical Research CouncilJapan Agency for Medical Research and DevelopmentNational Institute for Health Research (NIHR)National Institutes of HealthAcademy of Medical SciencesJapan Society for the Promotion of Science2483-2495.e26https://www.ebi.ac.uk/biostudies/studies/S-EPMC8169555biostudies-literatureUnknown160(7)<h4>Background & aims</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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 ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; JapaneGastroenterologyX Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.PMC8169555NIHR200243MR/T023848/1AMS-SGCL9-MellsG0800460MR/L001489/1R01 DK091823R01 DK123262Dillon JAllison JIchida TPicciotto AGervais ODias AYokosuka OButterworth JCordell HJHealey CWheatley NMattalia ADuga SGunter EGalaska RGrieve EKawai YTakaki HGrellier LGlenn STakaki AAndreone PAyres RKanda TWalker KHashimoto EKendall JKitchen PBird BDouds AOrpe JFuruta KMilani CFisher NYapp TLleo AColombo SYoung KColombo MLawlor CPatanwala IGleeson DFloreani AKoss KWhite NJoshita SSaoshiro TLipscomb GLevi SKoga MMiller RBrunetto MInvernizzi PShaukat SSalam ISiminovitch KABird GGocher DHoughton KAlvaro DGunasekera ABishop RQuinn MHines FSandford RNNasseri MNakao KMulvaney-Jones CGallagher SKaneko SColli AJapan PBC-GWAS ConsortiumSato TMitchison HYamashita TMcCorry RBramley PFeatherstone JDamant RSweeting HXiong MCoco BCrosignani ATakikawa HPateman HWhalley SLampertico PDonato FDavis ANagaoki YTanqueray ECarter MNakamura MKomori ANakamura HShinder BThornthwaite SOta HCursaro CMyers RRushbrook SAbe MAng YMarch LMills MMills PWarner KNakamura YNambela EMacFaul GDungca ECarnahan MPollock KTiribelli CTakeyama YKlass HValenti LSugawara YSaksena SMupudzi MAtkinson EBrookes MRamage JLiu XTamura SMathialahan TGorard DSanghi PYoong KHussaini HLee HJSaeed AVyas SSayer JDoyle HColloredo GAspinall RWatanabe YMells GFKokudo NHeneghan MCarbone MDelahooke TCongreave SYamauchi KMori AHarada MHarada KBrowning JOcker KShimada YGitahi JSugimoto RGordon HTyrer DShimada MBaxter GAffronti ATsunematsu SToniutto PShewan TBrighton JMalinverno FPrince MLeoni MHoeroldt BVerheyden JMigita KRosina FKeggans JOnji MForton DYamashiki NHankey LSouthern PNeal DMorini LBattezzati PMRamanaden DSilvestre VDyer SKobata TMizokami MItalian PBC Genetics Study GroupThomas CNcube NBurroughs AMann SShibata HBowles JHarvey RDawwas MPaton ACloudsdale RYamagiwa SElphick DCasey RUnitt EKent LMaehara YKent MFerrari CHynes AHogben KBooth JShepherd AIshibashi HAlmasio PLCasella GJuran BKawashima MCurtis HHigham ACowan MCzajkowski MHirano KNagasaki MCurtis JWood GSaha SMarley RMuratori LTakesaki EMuratori PStansfield GGreer SCox MMano YKikuchi MShearman JIdo AGee IElliott KKikuchi KGotto JKobayashi MNinkovic MMarra FWatson ATaniai MGiannini ECramp MSirdefield DCumlat LMillson CWooldridge HDouglass AIshida JAldersley MKomatsu TPeltekian KMandal ASen SMannami TBruno SSakai HBragazzi MTaylor-Robinson SCurrie LKomura TGershwin MEMukhopadhya AJing KEde RCroce LSCanadian-US PBC ConsortiumMurata KSenju MZeniya MCardinale VAlexander GBatham SDesousa PPrzemioslo RHarrison MTregonning JWalker EZuin MBray GRidpath JTakahashi HAiba YAli FGu XKamitsukasa HMarshall ESeward KTarocchi MGrant AShah AGraves LDucker SDas DWilhelmsen EGordon FSturgess RMetcalf JSpurdle KWright MWilliams ENaqvi AWilliams DLord SBaird YFairlamb HBrind ATaylor NWilliams BFoale CWright ADurant ETsubouchi HCollier JPatel MUK-PBC ConsortiumWright FHails JOhara YJain SEbinuma HAinsworth MUmemura TBroad AMaltby JStableforth WMorrison JBarnardo AHitomi YMarzioni MMaiden JRamakrishnan SDickson CWilliams STownshend PGeorge KPortincasa PAmos CD'Amato DSugi KJones DHamilton MAbiru SMacdonald CNaganuma APanter SOblak MLi AKatsushima SAbrahams RTsuruta SMathew RNetherton KGhosh DGess MHonda KLazaridis KWhiteman JMita EEastick AGreen MFarrington LHonda MKarmo MPearson SGray CHirashima NClement DKohn SSSubhani JShmueli UArcher EAmor KSinghal AClifford GStrazzabosco MNagaoka SSeldin MFFraser AMuscariu FUeno KEvans RLancaster NSinghal SShpuza EPereira SGupta HSlininger SFraser JCardamone GThorburn DMarriott SSrirajaskanthan RCazzagon NGibbins ABesley SUeno YOhira HKoda MWilkinson MTanaka AEvans CTripoli SCalvaruso VMason ALi ZJones JJones LGyawali PHamilton CJones RRyder SDJones SArio KShallcross CHayes MCrossey MLonghurst BColley JRaymode PHayashi SBraim DO'Donnell SEGrover BSpinzi GYagi SGooding IO'Donohoe LWalsh SParaboschi EMValliani TYoshizawa KSivaramakrishnan NBell AHimoto THobson LSadeghian JWatts GDali-Kemmery LMakita FGasem JO'Donnell DConder JMuro TNishida NCristoferi LMcNair ACollins CLim GGhent CShorrock CGunson BHovell CInnes CSimpson DKomeda TAustin AShi YHughes MYasunami MMartin KMclindon JWilkins JKapur KBoulton KChan PGoggin PKouno HRonca VMiele LGrattagliano IRigamonti CKordula JLoftus ATaketomi ARichardson PStafford LAmey IDavies MIchikawa TGerussi ABenedetti AFabris LBathgate ADuggan CSeike MFagiuoli SJones DELambourne VCowley CVinci MMcKay AAsselta RPitcher MChirag OFouracres ATanaka TTang RTibble JYagura MRolls SACotterill DNishimura HTokunaga KElia GMendall MWong VSNiro GACh'ng CLPremchand PArai KShidrawi RLee TPalegwala ABrown ARansford RSharer NLu YRees ILombard MMacNicol CIto MBrown CXie GAbouda GGalli ADesmennu SHolbrook BCiaccio ANeuberger JBarisani DHirschfield GYabuuchi ITan LYamamoto KButcher GYamamoto TPiotrowicz AMusselwhite JFoster GNaeshiro NRahman MUemoto SMisra SHirata KSoejima YPrasad GFoxton MMasaki NSakisaka SNarain MNakanuma YVan Duyvenvoorde GMancuso CPenn RDewhurst HFukushima NMorisco FAzzaroli FShimoda SMassironi SMatsushita KDrake IAla AShirabe KDolwani SKato MArinaga-Hino THolder SHarding TNgatchu TBanim PGrimley CNakamuta MHiguchi NChayama KCampbell SWinter LNikami TKing AWhatley GBrown JPalmer CAndriulli AYatsuhashi HFord CMiyake YFlahive KChilton AMorgan LfalseX Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.<h4>Background & aims</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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 ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japane2021-01-01T00:00:00Z2021 Jun2026-05-09T04:18:08.305Z2025-04-04T22:03:58.503ZS-EPMC81695553367574310.1053/j.gastro.2021.02.061