Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations.

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 × 10-7, 4.3 × 10-9) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.

Incidence of inflammatory bowel disease in Iceland 1995 - 2009. A nationwide population-based study.

OBJECTIVE: We analyzed the incidence of inflammatory bowel disease (IBD) in Iceland for the period 1995-2009. MATERIAL AND METHODS: New cases of ulcerative colitis (UC) and Crohn's disease (CD) were retrieved by thorough review of all small and large intestinal pathology reports with any type of inflammation from all the pathology departments in Iceland for the period 1995-2009. All suspicious new cases of IBD were then scrutinized retrospectively by examination of their clinical records. RESULTS: A total of 1175 cases of IBD were diagnosed, 884 UC, 279 CD and 12 IBD unclassified. The crude annual incidence of UC was 20.5/100,000, increasing from 18.1 the first 5-year period to 22.1 the last 5-year period. The crude annual incidence of CD was 6.5/100,000, 6.7 the first 5-year period and 6.6 the last 5-year period. CONCLUSIONS: This study shows statistically significant increase in the incidence of UC during the study period. The incidence of CD has however remained stable.

Colonic adenomas found via colonoscopy: yield and risk factors for high-grade dysplasia.

BACKGROUND AND AIMS: The adenoma-carcinoma sequence is the model for colorectal carcinoma (CRC) developing through high-grade dysplasia (HGD) to CRC. The aim was to assess prevalence and location of adenomas found during colonoscopy and risk factors for HGD. MATERIAL AND METHODS: A population-based study using all colonoscopies and polyp specimens registered between 2000 and 2004 in Iceland. Multiple logistic regression analysis was used to assess independent risk factors for HGD. RESULTS: A total of 3,315 adenomas were removed from 2,385 patients. Only 14.0% were >1 cm in size. HGD was found in 135 (4.1%) of the adenomas and tubulovillous/villous histology in 15.0%. The prevalence of adenomas in the 50- to 69-year age group was 15.5%, and 21.5% in the >or=70-year group. 60.9% of them were located distal to the splenic flexure. Independent risk factors for HGD were in the order of importance: size; multiplicity; tubulovillous/villous histology; location in rectum, and age. The prevalence of HGD in the group with an adenoma size of 0.6-1.0 cm was 4.1% and in the 40- to 69-year age group it was 3.7%. CONCLUSION: The study suggests a potential 15% yield per colonoscopy of adenomas in 50- to 69-year-olds. There is an appreciable risk of HGD in diminutive polyps and in middle age.