Author
Joseph A. Odin
Bio: Joseph A. Odin is an academic researcher from Icahn School of Medicine at Mount Sinai. The author has contributed to research in topics: Primary biliary cirrhosis & Liver transplantation. The author has an hindex of 28, co-authored 66 publications receiving 3072 citations.
Papers published on a yearly basis
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TL;DR: In this article, the authors present characteristics and subgroup analyses from the first 1257 patients enrolled in the study, and conclude that there are no differences in outcomes of patients with short vs long latency of DILI.
576 citations
TL;DR: This work discovers and validate six previously unknown risk loci for PBC and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine–cytokine pathways, for which relevant therapies exist.
Abstract: Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.
245 citations
Toronto Western Hospital1, University of Toronto2, University of Texas MD Anderson Cancer Center3, Mayo Clinic4, University of Alberta5, Pomeranian Medical University6, University of Calgary7, Icahn School of Medicine at Mount Sinai8, Virginia Commonwealth University9, Vilnius University10, Université de Montréal11, University of Florida12, North Shore-LIJ Health System13
TL;DR: Genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci and showed that a single variant accounts for the IRF5-TNPO3 association, confirming genetic overlap among such diseases.
Abstract: Katherine Siminovitch and colleagues report replication and fine-mapping studies for primary biliary cirrhosis. They identify three loci newly associated with susceptibility to this autoimmune liver disease.
203 citations
TL;DR: Toxin exposure may be a risk factor influencing the clustering of PBC cases and significant clusters of both PBC‐OLT and PSC‐MSSM were identified surrounding SFS.
201 citations
Wellcome Trust1, Mayo Clinic2, University of Kiel3, University of Oslo4, University of Oxford5, Karolinska Institutet6, Katholieke Universiteit Leuven7, University of Calgary8, University of Toronto9, University of Helsinki10, Charité11, University of Hamburg12, Hannover Medical School13, University of Bonn14, Heidelberg University15, University of Regensburg16, University of Amsterdam17, University of Groningen18, University of Gothenburg19, Medical University of Warsaw20, University of Barcelona21, University of Paris22, University of Cambridge23, NHS Blood and Transplant24, University of Padua25, University Health Network26, University of California, Davis27, Virginia Commonwealth University28, Icahn School of Medicine at Mount Sinai29, University of Pittsburgh30, Indiana University – Purdue University Indianapolis31, Cambridge University Hospitals NHS Foundation Trust32, University of Birmingham33
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.
Abstract: Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC.
200 citations
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Journal Article•
2,135 citations
TL;DR: The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis.
1,799 citations
TL;DR: PBC is a chronic cholestatic liver disease characterized by high-titer serum antimitochondrial autoantibodies (AMAs) and autoimmune-mediated destruction of small and medium-sized intrahepatic bile ducts as discussed by the authors.
1,289 citations
Ashley Beecham1, Nikolaos A. Patsopoulos2, Nikolaos A. Patsopoulos3, Dionysia K. Xifara4 +203 more•Institutions (73)
TL;DR: This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
Abstract: Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 10 × 10(-4)) In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 50 × 10(-8)), 3 of which we found after conditioning on previously identified variants Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals
1,197 citations
TL;DR: The mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC are discussed, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile Acid receptor 1 (TGR5).
Abstract: Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.
905 citations