was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/143933 doi: bioRxiv preprint first posted online Jul. 13, 2017; 2 Abstract:We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain-resident immune cells. Thus, while MS is most likely initially triggered by perturbation of peripheral immune responses the functional responses of microglia and other brain cells are also altered and may have a role in targeting an autoimmune process to the central nervous system.

To assess the feasibility of a prospective incidence study of inflammatory bowel disease (IBD), the registration methods and incidence figures during 1990 were evaluated. The study was a collaboration between 14 hospitals in an area of close to one million inhabitants. Common diagnostic criteria for ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis (IND) were established prior to the start of the study. There was an overall incidence rate for IBD of 19.3 per 10⁵ inhabitants, with 10.6 for UC, 5.1 for CD and 3.6 for IND.The age-specific incidence rates showed a peak between 25 and 34 years for UC and between 15 and 25 for CD. There was a male predominance for UC and a female preponderance for CD. These results are comparable with the previous registrations in western and northern areas of Norway.

Enzyme activity was studied in relationship to histological changes in biopsy specimens removed after resection from patients with inflammatory bowel disease. Glucose-6-phosphate dehydrogenase (G6-PDH) and lactate dehydrogenase activities were measured in homogenates from 276 large-intestinal biopsy specimens, classified histologically in accordance with grade of inflammation and dysplasia. The mean activity of both enzymes was highest in the presence of dysplasia; however, only G6-PDH activity seemed independent of inflammatory changes. In the seven patients with dysplasia both enzyme activities were significantly raised in segments with dysplasia, compared with those without. The results support the use of dysplasia as a marker of premalignancy and may suggest a role for measurements of enzyme activity in the evaluation of patients with ulcerative colitis.

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Epithelial dysplasia was found in the large intestine of 8 of 15 patients with ulcerative colitis operated on between 1980 and 1982. In six of eight patients, dysplasia was found in the cecum and ascending colon, in one of eight in the descending or sigmoid colon, and in four of eight in the rectum. None of the five carcinomas in three patients were located in the sigmoid colon or rectum. The age of onset was much lower, 19 +/- 7 years, and the duration of colitis longer, 15 +/- 7 years, for the group with dysplasia compared with that without dysplasia, 37 +/- 18 and 4 +/- 3 years, respectively. Our study indicates that malignant transformation may frequently occur in the proximal colon and emphasizes the need for total colonoscopy with multiple biopsies in the evaluation of patients with long-standing ulcerative colitis.