Transethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals not only shared but also ethnicity-specific disease associations.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such as delineation could not be made because of tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a transethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analyzed the physicochemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we not only identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time. For the majority of the IBD risk loci, the direction and magnitude of effect are consistent in European and non-European cohorts. Nevertheless, we observe genetic heterogeneity between divergent populations at several established risk loci driven by differences in allele frequency (NOD2) or effect size (TNFSF15 and ATG16L1) or a combination of these factors (IL23R and IRGM). Our results provide biological insights into the pathogenesis of IBD and demonstrate the usefulness of trans-ancestry association studies for mapping loci associated with complex diseases and understanding genetic architecture across diverse populations.

Morning report: a survey of Iranian senior faculty attitudes.

Morning report (MR) is a universal component of internal medicine training. Despite its omnipresence, little is known about senior faculty attitudes toward MR. We aimed to survey expert attitudes towards MR. Using an 85-item self-administered questionnaire, we made a survey of medical education-trained faculty members (FMs) who participated in and presented articles at the Seventh National Iranian Congress on Medical Education, 12-15 November 2005, Tabriz, Iran, on the processes of teaching and learning during MR (n=175). Among the 111 FMs (63.4%) who completed the survey, education was the most frequently cited goal of the MR. Clinical wisdom and the ability to expand a resident's differential diagnosis skills were the attributes most often proposed as essential for the FMs. Respondents believed the FM in cooperation with the senior resident of the last duty (41%) or the senior resident of the last duty alone (40%) should select the presenting cases. The study participants stated that 41% of the MR should be spent discussing common cases, 33% in the area of expertise of the FM and 26% in discussing rare or interesting cases. A common opinion was that treatment recommendations should be based on the medical literature. In terms of the educational impact of activities during the MR, listing differential diagnoses and bedside visits to examine unique findings scored the highest. Education as the main goal of the MR can best be achieved by expanding residents' skills in differential diagnosis and in making decisions using an evidence-based, self-directed method.