that demonstrated genome-wide significant evidence for association were added to the replication candidate list. rs6426833, rs2395185 and rs1558744 were genotyped by Pyrosequencing (Biotage AB, Uppsala, Sweden) at the University of Pittsburgh. SNPs on the replication candidate list that had designable Sequenom iPlex (Sequenom, San Diego, CA) assays and could be multiplexed in three oligonucleotide pools were genotyped on the Sequenom MassArray platform at the University of Pittsburgh (North American samples and some of the Italian sample genotyping) and the Montreal Heart Institute (Italian samples). Samples with high genotyping failure rates were attempted a second time. Data management and quality control filtering are described in the Supplementary Methods online. Association evidence in the two replication samples was assessed using the Cochran-Mantel-Haenszel (CMH) test, and the Fisher method was used to combine UC GWAS GEM P values and replication CMH P values. SNPs with combined P values < 5×10−8 were considered to have genome-wide significant evidence for association27. SNPs with genome-wide significant evidence for association in the UC GWAS and CMH P values < 0.05 in the replication samples were considered to have confirmed association with UC.
