The UK iCHIP study of PBC was completed in 2012, as part of the Wellcome Trust Case Control Consortium(WTCCC3).

In this study, 2,861 PBC cases recruited via the UK-PBC Consortium and 8,514 UK population controls were genotyped using the “Immunochip”, an Illumina iSelect HD Custom Genotyping BeadChip consisting of 196,524 variants at 186 known autoimmune risk loci.

This study confirmed previously-identified PBC risk loci and identified three additional PBC risk loci. Classical HLA alleles were imputed from dense SNP genotype data across the HLA region and four HLA haplotypes were shown to be independently associated with disease, including the risk haplotype, DRB1*04:04-DQB1*03:02, which had not been identified in previous studies.

The study also identified multiple independent associations at five loci, ranging in frequency from rare to common. The paper reporting this study was published in Nature Genetics, Oct 2012. The dataset is available on request.


Manhattan plot from the UK iCHIP study of PBC


The figure shows the Manhattan plot from the UK iCHIP study of PBC. Newly-identified risk loci are highlighted in blue. Loci with more than one independent signal are highlighted in red. The horizontal red line indicates the genome-wide significance threshold of P=5E-8. The peak on chromosome 6 is the HLA region.