title: Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis.
abstract: We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 x 10(-4)) identified in a previous genome-wide association study. Combined analysis of the genome-wide association and replication datasets identified IRF5-TNPO3 (combined P = 8.66 x 10(-13)), 17q12-21 (combined P = 3.50 x 10(-13)) and MMEL1 (combined P = 3.15 x 10(-8)) as new primary biliary cirrhosis susceptibility loci. Fine-mapping studies showed that a single variant accounts for the IRF5-TNPO3 association. As these loci are implicated in other autoimmune conditions, these findings confirm genetic overlap among such diseases.
authors.affiliation: Liver Centre, Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: Gideon M
authors.initials: GM
authors.lastname: Hirschfield
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Liu
authors.forename: Younghun
authors.initials: Y
authors.lastname: Han
authors.forename: Ivan P
authors.initials: IP
authors.lastname: Gorlov
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Brian D
authors.initials: BD
authors.lastname: Juran
authors.forename: Catalina
authors.initials: C
authors.lastname: Coltescu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mason
authors.forename: Piotr
authors.initials: P
authors.lastname: Milkiewicz
authors.forename: Robert P
authors.initials: RP
authors.lastname: Myers
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Odin
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.forename: Danute
authors.initials: D
authors.lastname: Speiciene
authors.forename: Catherine
authors.initials: C
authors.lastname: Vincent
authors.forename: Cynthia
authors.initials: C
authors.lastname: Levy
authors.forename: Peter K
authors.initials: PK
authors.lastname: Gregersen
authors.forename: Jinyi
authors.initials: J
authors.lastname: Zhang
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Lazaridis
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Siminovitch
mesh_terms: D016022:Case-Control Studies; D005796:Genes; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics*; D012307:Risk Factors