Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis.
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.
Hirschfield
Gideon M
GM
Liver Centre, Toronto Western Hospital, Toronto, Ontario, Canada.
Liu
Xiangdong
X
Han
Younghun
Y
Gorlov
Ivan P
IP
Lu
Yan
Y
Xu
Chun
C
Lu
Yue
Y
Chen
Wei
W
Juran
Brian D
BD
Coltescu
Catalina
C
Mason
Andrew L
AL
Milkiewicz
Piotr
P
Myers
Robert P
RP
Odin
Joseph A
JA
Luketic
Velimir A
VA
Speiciene
Danute
D
Vincent
Catherine
C
Levy
Cynthia
C
Gregersen
Peter K
PK
Zhang
Jinyi
J
Heathcote
E Jenny
EJ
Lazaridis
Konstantinos N
KN
Amos
Christopher I
CI
Siminovitch
Katherine A
KA
D016022:Case-Control Studies; D005796:Genes; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics*; D012307:Risk Factors