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The A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness.

As no population-based study has investigated the susceptibility and disease course of COVID-19 among patients with inflammatory bowel diseases [IBD], we aimed to investigate this topic in a population-based setting.

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

Understanding the biological changes that precede a diagnosis of inflammatory bowel disease (IBD) could facilitate pre-emptive interventions, including risk factor modification, but this pre-clinical phase of disease remains poorly characterized. Using measurements from 17 hematological and biochemical parameters taken up to 10 years before diagnosis in over 20,000 IBD patients and population controls, we address this at massive scale. We observe widespread significant changes in multiple biochemical and hematological parameters that occur up to 8 years before diagnosis of Crohn's disease (CD) and up to 3 years before diagnosis of ulcerative colitis. These changes far exceed previous expectations regarding the length of this pre-diagnostic phase, revealing an opportunity for earlier intervention, especially in CD. In summary, using a nationwide, case-control dataset-obtained from the Danish registers-we provide a comprehensive characterization of the hematological and biochemical changes that occur in the pre-clinical phase of IBD.

Body mass index (BMI) is associated with increased future risk of inflammatory bowel disease(IBD) particularly Crohn's disease(CD), where associations with high and low BMI have been observed. Most studies are based on adult women. We aimed to explore the impact of BMI in men entering adult life on their long-term risk of developing IBD. A total of 377,957 men born during 1939-1959, with BMI measured at draft boards at mean age 19, were followed from 1977, or time of examination, to end of 2015. Risk of IBD was assessed using Cox regression. During 13 million person-years of follow-up, 1,523 developed CD and 3,323 UC. Using normal weight as reference, for CD the following HRs were observed: BMI < 18.5, 1.35; 95% CI, 1.12-1.62, BMI 25-29.9; 0.83; 95% CI, 0.68-1.02. and BMI > 30 1.20; 95% CI, 0.75-1.90). The increased risk of CD in underweight was maintained up until age 60 not explained by known effects of smoking. For UC, minor inverse associations were observed. Restricted cubic splines revealed a U-shape association between BMI and CD, but not UC. Low BMI of men entering adult life is associated with an increased incidence of CD and UC up to 40 years later.

Background: Elevated eosinophils in COPD is recognized as a potential risk factor for exacerbations, but the prognostic role of elevated eosinophils during exacerbations of COPD is unclear. We investigated short-term and long-term outcomes in patients with exacerbations of eosinophilic phenotype, compared with patients with low blood eosinophils. Methods: A single-centre retrospective study of all patients admitted for a COPD exacerbation to Bispebjerg University Hospital in 2010-2011 was established by linking inpatient data with national patient and prescription registries, with a three-year follow-up period. Elevated eosinophils were defined as a blood eosinophil level at admission of ≥0.30 × 109 cells/L. Results: A total of 811 patients were included; 13.2% had an eosinophilic exacerbation. The eosinophilic group had less need for non-invasive ventilation, shorter inpatient stay, and lower in-hospital mortality, compared to the non-eosinophilic group. However, the eosinophilic and non-eosinophilic groups showed similar risks of readmission (incidence rate ratio[95], 0.99 [0.73-1.36]). Three-year mortality was high in both groups, although lower in the eosinophilic group (40% vs. 54%, p = 0.006). Conclusions: COPD exacerbations in patients with high blood eosinophil have a better short-term prognosis without higher risk of subsequent exacerbation. Eosinophilic exacerbations have also a lower three-year mortality.

There is increased risk of several malignancies in inflammatory bowel disease (IBD). However, evidence regarding risk of cervical cancer in IBD is conflicting. We aimed to investigate the risk of cervical cancer in IBD by undertaking a systematic review and meta-analysis of unselected, population-based studies.

Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported.

We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9.

Because the incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing, knowledge of the long-term risk of cancer in this patient population is required.

Based on animal studies, n-3 polyunsaturated fatty acids (PUFAs) have been suggested to lower the risk of obesity and inflammation. We aimed to investigate if, among humans, intake of n-3 PUFAs was associated with i) total body fat, ii) body fat distribution and iii) obesity-related inflammatory markers.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), affect millions of people worldwide with increasing incidence.