Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis.

Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis.

Nature genetics (2010-07-20)

Gideon M Hirschfield, Xiangdong Liu, Younghun Han, Ivan P Gorlov, Yan Lu, Chun Xu, Yue Lu, Wei Chen, Brian D Juran, Catalina Coltescu, Andrew L Mason, Piotr Milkiewicz, Robert P Myers, Joseph A Odin, Velimir A Luketic, Danute Speiciene, Catherine Vincent, Cynthia Levy, Peter K Gregersen, Jinyi Zhang, E Jenny Heathcote, Konstantinos N Lazaridis, Christopher I Amos, Katherine A Siminovitch

PMID20639879

摘要

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.