Although genome-wide association studies and fine mapping have identified 39 non-HLA loci associated with celiac disease (CD), it is difficult to pinpoint the functional variants and susceptibility genes in these loci. We applied integrative approaches to annotate and prioritize functional single nucleotide polymorphisms (SNPs), genes and pathways affected in CD. CD-associated SNPs were intersected with regulatory elements categorized by the ENCODE project to prioritize functional variants, while results from cis-expression quantitative trait loci (eQTL) mapping in 1469 blood samples were combined with co-expression analyses to prioritize causative genes. To identify the key cell types involved in CD, we performed pathway analysis on RNA-sequencing data from different immune cell populations and on publicly available expression data on non-immune tissues. We discovered that CD SNPs are significantly enriched in B-cell-specific enhancer regions, suggesting that, besides T-cell processes, B-cell responses play a major role in CD. By combining eQTL and co-expression analyses, we prioritized 43 susceptibility genes in 36 loci. Pathway and tissue-specific expression analyses on these genes suggested enrichment of CD genes in the Th1, Th2 and Th17 pathways, but also predicted a role for four genes in the intestinal barrier function. We also discovered an intricate transcriptional connectivity between CD susceptibility genes and interferon-γ, a key effector in CD, despite the absence of CD-associated SNPs in the IFNG locus. Using systems biology, we prioritized the CD-associated functional SNPs and genes. By highlighting a role for B cells in CD, which classically has been described as a T-cell-driven disease, we offer new insights into the mechanisms and pathways underlying CD.

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The objective of this study was to assess the effect of relaxing massage on the heart rate (HR) and heart rate variability (HRV) in young racehorses during their first racing season. In the study, 72 Purebred Arabian racehorses were included. The study was implemented during the full race season. The horses from control and experimental groups were included in regular race training 6 days a week. The horses from the experimental group were additionally subject to the relaxing massage 3 days a week during the whole study. HR and HRV were assumed as indicators of the emotional state of the horses. The measurements were taken six times, every 4-5 weeks. The HRV parameters were measured at rest, during grooming and saddling the horse and during warm-up walking under a rider. The changes of the parameters throughout the season suggest that the relaxing massage may be effectively used to make the racehorses more relaxed and calm. Moreover, the horses from the experimental group had better race performance records.