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- Rosendahl, J, et al.
(författare)
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Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:10, s. 1855-1863
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus.Design1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used.ResultsWe replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk.ConclusionAn inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.
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| 3. |
- Lowden, Arne, 1957-, et al.
(författare)
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Delayed Sleep in Winter Related to Natural Daylight Exposure among Arctic Day Workers
- 2018
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Ingår i: Clocks & Sleep. - : MDPI AG. - 2624-5175. ; 1:1, s. 105-116
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Tidskriftsartikel (refereegranskat)abstract
- Natural daylight exposures in arctic regions vary substantially across seasons. Negative consequences have been observed in self-reports of sleep and daytime functions during the winter but have rarely been studied in detail. The focus of the present study set out to investigate sleep seasonality among indoor workers using objective and subjective measures. Sleep seasonality among daytime office workers (n = 32) in Kiruna (Sweden, 67.86° N, 20.23° E) was studied by comparing the same group of workers in a winter and summer week, including work and days off at the weekend, using actigraphs (motion loggers) and subjective ratings of alertness and mood. Actigraph analyses showed delayed sleep onset of 39 min in winter compared to the corresponding summer week (p < 0.0001) and shorter weekly sleep duration by 12 min (p = 0.0154). A delay of mid-sleep was present in winter at workdays (25 min, p < 0.0001) and more strongly delayed during days off (46 min, p < 0.0001). Sleepiness levels were higher in winter compared to summer (p < 0.05). Increased morning light exposure was associated with earlier mid-sleep (p < 0.001), while increased evening light exposure was associated with delay (p < 0.01). This study confirms earlier work that suggests that lack of natural daylight delays the sleep/wake cycle in a group of indoor workers, despite having access to electric lighting. Photic stimuli resulted in a general advanced sleep/wake rhythm during summer and increased alertness levels.
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