Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.
ABSTRACT In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻⁸) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC.
Article: Genome-wide association study identifies loci on 12q24 and 13q32 associated with Tetralogy of Fallot.[show abstract] [hide abstract]
ABSTRACT: We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot, using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P=1.4×10(-7)) and replicated convincingly (P=3.9×10(-5)) in 798 cases and 2931 controls (per allele OR=1.27 in replication cohort, P=7.7×10(-11) in combined populations). SNPs in the glypican 5 gene (GPC5) on chromosome 13q32 were also associated (P=1.7×10(-7)) and replicated convincingly (P=1.2×10(-5)) in 789 cases and 2927 controls (per allele OR=1.31 in replication cohort, P=3.03×10(-11) in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of Tetralogy of Fallot.Human Molecular Genetics 01/2013; · 7.64 Impact Factor