Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

Abstract

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10–11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10–10, OR = 1.63) and 17q12-21 (P = 1.7 × 10–10, OR = 1.38).

Genetics and epigenetics in the pathogenesis of primary biliary cholangitis

“…The second GWAS [36] confirmed the existence of additional risk loci, including interferon regulatory factor 5 (IRF5), transportin 3 (TNPO3), and transcription factor Spi-B (SPIB) encoding a transcription factor involved in B-cell receptor signaling and T-cell lineage decisions. A subsequent GWAS from Japan showed that tumor necrosis factor superfamily, member 15 (TNFSF15) and POU domain class 2-associating factor 1 (POU2AF1) genes also constituted novel risk loci in Japanese patients with PBC, and a recent GWAS of a Han Chinese population found the highest association was between TNFSF15 and PBC.…”

“…Among the SNPs previously reported to be associated with susceptibility to PBC, only HLA has been consistently linked to the disease in distinct patient cohorts across ethnicities as depicted by many significant dots on genome-wide Manhattan plots of GWASs [34][35][36][37][38][39][40][41][42][43].…”

Emerging Issues in the Immunopathogenesis, Diagnosis and Clinical Management of Primary Biliary Cirrhosis Associated with Systemic Sclerosis

“…Non-HLA regions have also been identified in SSc, and include STAT4 (Agarwal & Reveille, 2010), IRF5 (Agarwal & Reveille, 2010), BANK1, TNSF4, TBX21, IL-23R , and C8orf13-BLK among others (Agarwal & Reveille, 2010). Overlapping PBC/SSc genes include HLA-DRB1, DQA1, DQB1, IRF5, and STAT4, although it should be noted that DR11, which is positively associated with SSc, is considered protective in PBC (Agarwal & Reveille, 2010;Liu et al, 2010). …”

Explosion of autoimmune diseases and the mosaic of old and novel factors

“…For example, the increased concordance in monozygotic, as compared with dizygotic, twins and the increased prevalence of affected family members have been documented in many diseases. 43 The most potent genetic influence on autoimmunity is via the major histocompatibility complex (MHC), although non-MHC-susceptible alleles have also been documented, 44,45 and a plausible role for gene therapies in autoimmune diseases has been suggested. 20 In this issue, Proal et al utilize metagenomics to present a novel approach to deciphering the secrets of human autoimmunity and a promising new approach to treating autoimmune diseases.…”