International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

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

What, not just salad and veg? Consumer testing of the eatwell week

Objective: To test the appeal of the eatwell week, a nutritionally balanced 7 d menu which satisfies nutritional guidelines of the Food Standards Agency in Scotland; determine the clarity and understanding of the main messages; and gather views on the usability and acceptability of the eatwell week resource format.&lt;p&gt;&lt;/p&gt; Design: Focus group discussions with consumers and health professionals.&lt;p&gt;&lt;/p&gt; Setting: Four locations across the UK.&lt;p&gt;&lt;/p&gt; Results: The eatwell week was considered realistic by consumers as it contained foods they recognised and already ate. A preconceived idea had been that there would be more fruit and vegetables and fewer ‘treats’. Consumers found the recipes simple and lack of cooking skills was not an apparent barrier. However, the message of ‘balance’ was poorly understood. Consumers often lacked the knowledge to make informed substitutions in the week. Both the general public and some health professionals felt the menu contained too much carbohydrate. Health professionals felt it was unclear who the eatwell week was intended for and what purpose it served.&lt;p&gt;&lt;/p&gt; Conclusions: Use of familiar foods and the provision of simple, easy-to-follow recipes have the potential to overcome some barriers to healthy eating encountered by the general public and encourage improvements in dietary intakes. The eatwell week shows promise as a resource to facilitate implementation of the principles of the eatwell plate and supports government priorities and policies for health

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.

BACKGROUND & AIMS: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. METHODS: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). RESULTS: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10(-4), with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10(-6); odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10(-8)), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10(-9); OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). CONCLUSIONS: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted versio