Andreas Teufel

TL;DR: Liver samples from morbidly obese patients with all stages of NAFLD and controls were analyzed by array-based DNA methylation and mRNA expression profiling, providing an example of treatment-induced epigenetic organ remodeling in humans.

Abstract: Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.

TL;DR: This study undertook the largest genome-wide association study of PSC and identified four new genome- wide significant loci, with the most associated SNP at one locus predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A.

TL;DR: On a pathway level, gene expression patterns in livers of mice on the high-fat diet were associated more closely with human fatty liver disease than other models.

TL;DR: By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, this work was able to detect two novel risk loci at genome‐wide significance levels that may represent previously unexplored aspects of PSC pathogenesis.