Open AccessVariants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis
Author(s) -
Gideon M. Hirschfield,
Xiangdong Liu,
Younghun Han,
Ivan P. Gorlov,
Yan Lü,
Xu Chun,
Yao Lu,
Wei Chen,
Brian D. Juran,
Catalina Coltescu,
Andrew L. Mason,
Piotr Milkiewicz,
Robert P. Myers,
Joseph A. Odin,
Velimir A. Luketic,
Danutė Speičienė,
Catherine Vincent,
Cynthia Levy,
Peter K. Gregersen,
Jinyi Zhang,
E. Jenny Heathcote,
Konstantinos N. Lazaridis,
Christopher I. Amos,
Katherine A. Siminovitch
Publication year - 2010
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/ng.631
Subject(s) - primary biliary cirrhosis , biology , genome wide association study , irf5 , genetic association , genetics , cirrhosis , single nucleotide polymorphism , gene , medicine , immunology , genotype , transcription factor , interferon regulatory factors
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.