Inflammatory bowel diseases are chronic gastrointestinal inflammatory disorders that affect millions of people worldwide. Genome-wide association studies have identified 200 inflammatory bowel ...disease-associated loci, but few have been conclusively resolved to specific functional variants. Here we report fine-mapping of 94 inflammatory bowel disease loci using high-density genotyping in 67,852 individuals. We pinpoint 18 associations to a single causal variant with greater than 95% certainty, and an additional 27 associations to a single variant with greater than 50% certainty. These 45 variants are significantly enriched for protein-coding changes (n = 13), direct disruption of transcription-factor binding sites (n = 3), and tissue-specific epigenetic marks (n = 10), with the last category showing enrichment in specific immune cells among associations stronger in Crohn's disease and in gut mucosa among associations stronger in ulcerative colitis. The results of this study suggest that high-resolution fine-mapping in large samples can convert many discoveries from genome-wide association studies into statistically convincing causal variants, providing a powerful substrate for experimental elucidation of disease mechanisms.
Summary
Background
Equine recurrent uveitis (ERU) has been associated with Leptospira spp. infection. No information exists concerning the prevalence of Leptospira‐associated ERU in Belgium and about ...the sensitivity of detection of Leptospira in different ocular media.
Objectives
To establish the prevalence of intraocular Leptospira spp. in ERU‐affected and healthy eyes of horses examined at the Equine Clinic of the University of Liège by real‐time PCR and to compare the results of the aqueous and vitreous humour of the same eye.
Study design
Cross‐sectional.
Methods
Sixty‐six eyes from 59 client‐owned horses with a diagnosis of equine recurrent uveitis (ERU‐group) were studied from May 2015 to December 2017. Fifty healthy eyes from 28 euthanised horses for unrelated reasons examined during the same period were included in the control group. Intraocular fluids (aqueous and/or vitreous humours) from ERU‐affected eyes were sampled and analysed by real‐time PCR for Leptospira spp. Aqueous and vitreous humours from the control group were processed in the same way.
Results
Both groups were comparable regarding age, sex, eye sampled (OS/OD), humours sampled (aqueous/vitreous humour) but not regarding breeds, with an over‐representation of Warmbloods and Appaloosas in the ERU‐group. The prevalence of Leptospira spp. was 30.3% (20/66 eyes) in the ERU‐group. Leptospira spp. DNA was identified in 11 aqueous and 17 vitreous humours with eight horses testing positive in both humours, nine horses testing positive for vitreous humour alone and third horses for aqueous humour alone. The phi‐correlation between aqueous and vitreous humour Leptospira‐PCR results is 0.47 suggesting a low association. All the control eyes were negative.
Main limitations
The diagnostic method selected for this study (lipL32 qPCR) did not allow identification of the serovars.
Conclusions
Leptospirosis is a potential cause of ERU in Belgium. Testing both intraocular media is advised whenever possible.
The Summary is available in Spanish – see Supporting Information
GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes ...that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
This study aimed to evaluate the effect of sex and sub-zero storage temperature on the microbial and oxidative stability of Belgian Blue beef packed in a high-oxygen atmosphere after different ageing ...times. Longissimus thoracis et lumborum from Belgian Blue young bulls and cull cows were aged at −1 or 4 °C for 80 days in vacuum. Every 20 days, samples were repackaged in a high-oxygen atmosphere (70/30% O2/CO2) and stored for 7 days (2 days at 4 °C + 5 days at 8 °C). Ageing at −1 °C had a protective effect against the growth of lactic acid bacteria and Enterobacteriaceae and myoglobin oxidation. Brochothrix thermosphacta was the limiting parameter for ageing longer than 20 days at −1 °C, permitting a subsequent 7-day shelf-life in a high-oxygen atmosphere. Meat from young bulls was more sensitive to oxidation than meat from cull cows. Extending Belgian Blue meat ageing for >20 days had a negative impact on retail shelf-life.
•Ageing at −1 °C can improve microbial and colour stability of meat.•Meat from young bulls is more sensitive to oxidation than meat from cull cows.•Brochothrix thermosphacta growth limits the length of beef ageing at −1 °C.•Ageing Belgian Blue meat for >20 days is not recommended for retail display.
This study was aimed at assessing the pigment and lipid stability and characterising the microbial ecology by classical methods and metagenetics in beef with an extremely long shelf-life. Bovine ...longissimus thoracis et lumborum subprimals from different origins (Australia, Brazil, Ireland, and United Kingdom), displaying a shelf-life from 35 to 140 days in vacuum packaging, were aged at −1 (subzero storage) or a −1/+4°C two-level stepwise scheme. At different times, samples were repackaged under a high-oxygen atmosphere (70/30% O2/CO2) and stored at 4°C for two days and then 8°C for five days to simulate retail distribution. Subzero storage inhibited the growth of total aerobic mesophilic flora and Enterobacteriaceae during ageing in vacuum (p<0.001). During simulated retail distribution, the shelf-life was limited by metmyoglobin formation and excessive lactic acid bacteria growth. Classical microbiological methods underestimated the lactic acid bacteria count. Nonetheless, metagenetics evidenced, specifically in Australian samples, high proportions of Carnobacterium maltaromaticum, a lactic acid bacterium that may have contributed to the extremely long shelf-life of Australian beef.
Abstract
Study Objectives
Sleep disturbances and genetic variants have been identified as risk factors for Alzheimer’s disease (AD). Our goal was to assess whether genome-wide polygenic risk scores ...(PRS) for AD associate with sleep phenotypes in young adults, decades before typical AD symptom onset.
Methods
We computed whole-genome PRS for AD and extensively phenotyped sleep under different sleep conditions, including baseline sleep, recovery sleep following sleep deprivation, and extended sleep opportunity, in a carefully selected homogenous sample of 363 healthy young men (22.1 years ± 2.7) devoid of sleep and cognitive disorders.
Results
AD PRS was associated with more slow-wave energy, that is, the cumulated power in the 0.5–4 Hz EEG band, a marker of sleep need, during habitual sleep and following sleep loss, and potentially with larger slow-wave sleep rebound following sleep deprivation. Furthermore, higher AD PRS was correlated with higher habitual daytime sleepiness.
Conclusions
These results imply that sleep features may be associated with AD liability in young adults, when current AD biomarkers are typically negative, and support the notion that quantifying sleep alterations may be useful in assessing the risk for developing AD.
This study aimed to compare the effect of muscle type, aging technique, and aging time on the oxidative stability of beef packed in high‐oxygen atmosphere. Longissimus thoracis et lumborum (LTL) and ...rectus femoris (RF) muscles from Belgian Blue cows were vacuum aged (VA) or aged on the carcass (CA) for 7 days. Then, they were stored under vacuum at −1 °C for up to 28 days. At different times, samples were repackaged under a high‐oxygen atmosphere and stored at 4 °C for 7 days. The following parameters were evaluated: color, metmyoglobin %, fat content, fatty acid profile, lipid oxidation, metmyoglobin reducing activity (MRA), α‐tocopherol content, and antioxidant enzymes activity. The sensitivity of meat to oxidation was influenced by muscle type (RF > LTL), aging technique (VA > CA), aging time (35 > 21 > 7 days), and display time (7 > 0 days), and could be related to MRA and antioxidant enzymes activity.
Practical applications
High‐oxygen modified atmosphere packaging is often used by the meat industry at the retail level to maintain an attractive color in fresh meat. Nevertheless, this kind of packaging can promote early discoloration, lipid oxidation, and sensory changes. In this way, the meat sector seeks solutions to prevent meat oxidation and to extend the shelf‐life of beef packed in high‐oxygen atmosphere. The results obtained in this study show that aging on the carcass before cutting and further vacuum storage can limit the oxidation of meat when it is repacked in a high‐oxygen atmosphere. Moreover, this technique shows an additional advantage when handling muscles which are sensitive to oxidation, including rectus femoris. Therefore, the present work provides new knowledge that contributes to the understanding of the oxidative capacity of meat under different conditions and the development of appropriate strategies for beef aging and preservation.
Summary
We herein describe the realization of a genome‐wide association study for scrotal hernia and cryptorchidism in Norwegian and Belgian commercial pig populations. We have used the transmission ...disequilibrium test to avoid spurious associations due to population stratification. By doing so, we obtained genome‐wide significant signals for both diseases with SNPs located in the pseudo‐autosomal region in the vicinity of the pseudo‐autosomal boundary. By further analyzing these signals, we demonstrate that the observed transmission disequilibria are artifactual. We determine that transmission bias at pseudo‐autosomal markers will occur (i) when analyzing traits with sex‐limited expression and (ii) when the allelic frequencies at the marker locus differ between X and Y chromosomes. We show that the bias is due to the fact that (i) sires will preferentially transmit the allele enriched on the Y (respectively X) chromosome to affected sons (respectively daughters) and (ii) dams will appear to preferentially transmit the allele enriched on the Y (respectively X) to affected sons (respectively daughters), as offspring inheriting the other allele are more likely to be non‐informative. We define the conditions to mitigate these issues, namely by (i) extracting information from maternal meiosis only and (ii) ignoring trios for which sire and dam have the same heterozygous genotype. We show that by applying these rules to scrotal hernia and cryptorchidism, the pseudo‐autosomal signals disappear, confirming their spurious nature.
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