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- Li, X, et al.
(författare)
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MR-PheWAS: exploring the causal effect of SUA level on multiple disease outcomes by using genetic instruments in UK Biobank
- 2018
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 77:7, s. 1039-1047
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate the role of serum uric acid (SUA) level in a broad spectrum of disease outcomes using data for 120 091 individuals from UK Biobank.MethodsWe performed a phenome-wide association study (PheWAS) to identify disease outcomes associated with SUA genetic risk loci. We then implemented conventional Mendelianrandomisation (MR) analysis to investigate the causal relevance between SUA level and disease outcomes identified from PheWAS. We next applied MR Egger analysis to detect and account for potential pleiotropy, which conventional MR analysis might mistake for causality, and used the HEIDI (heterogeneity in dependent instruments) test to remove cross-phenotype associations that were likely due to genetic linkage.ResultsOur PheWAS identified 25 disease groups/outcomes associated with SUA genetic risk loci after multiple testing correction (P<8.57e-05). Our conventional MR analysis implicated a causal role of SUA level in three disease groups: inflammatory polyarthropathies (OR=1.22, 95% CI 1.11 to 1.34), hypertensive disease (OR=1.08, 95% CI 1.03 to 1.14) and disorders of metabolism (OR=1.07, 95% CI 1.01 to 1.14); and four disease outcomes: gout (OR=4.88, 95% CI 3.91 to 6.09), essential hypertension (OR=1.08, 95% CI 1.03 to 1.14), myocardial infarction (OR=1.16, 95% CI 1.03 to 1.30) and coeliac disease (OR=1.41, 95% CI 1.05 to 1.89). After balancing pleiotropic effects in MR Egger analysis, only gout and its encompassing disease group of inflammatory polyarthropathies were considered to be causally associated with SUA level. Our analysis highlighted a locus (ATXN2/S2HB3) that may influence SUA level and multiple cardiovascular and autoimmune diseases via pleiotropy.ConclusionsElevated SUA level is convincing to cause gout and inflammatory polyarthropathies, and might act as a marker for the wider range of diseases with which it associates. Our findings support further investigation on the clinical relevance of SUA level with cardiovascular, metabolic, autoimmune and respiratory diseases.
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- Tympakianaki, Athina, et al.
(författare)
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Real-time merging traffic control for throughput maximization at motorway work zones
- 2014
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Ingår i: Transportation Research Part C. - : Elsevier BV. - 0968-090X .- 1879-2359. ; 44, s. 242-252
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Tidskriftsartikel (refereegranskat)abstract
- Work zones on motorways necessitate the drop of one or more lanes which may lead to significant reduction of traffic flow capacity and efficiency, traffic flow disruptions, congestion creation, and increased accident risk. Real-time traffic control by use of green-red traffic signals at the motorway mainstream is proposed in order to achieve safer merging of vehicles entering the work zone and, at the same time, maximize throughput and reduce travel delays. A significant issue that had been neglected in previous research is the investigation of the impact of distance between the merge area and the traffic lights so as to achieve, in combination with the employed real-time traffic control strategy, the most efficient merging of vehicles. The control strategy applied for real-time signal operation is based on an ALINEA-like proportional-integral (PI-type) feedback regulator. In order to achieve maximum performance of the control strategy, some calibration of the regulator's parameters may be necessary. The calibration is first conducted manually, via a typical trial-and-error procedure. In an additional investigation, the recently proposed learning/adaptive fine-tuning (AFT) algorithm is employed in order to automatically fine-tune the regulator parameters. Experiments conducted with a microscopic simulator for a hypothetical work zone infrastructure, demonstrate the potential high benefits of the control scheme.
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- Herolf, Gunilla, et al.
(författare)
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Självstyrelser i Norden i ett fredsperspektiv : Färöarna, Grönland och Åland
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- Norden har erfarenheter av fredlig samlevnad i 200 år som är värda att lyfta fram och dra lärdomar av. Det finns ett stort internationellt intresse för dessa erfarenheter, inklusive erfarenheter av territoriell självstyrelse. I en värld som ter sig alltmer oroande ses Färöarnas, Grönlands och Ålands självstyrelser som värdefulla att studera ur ett konfliktlösande perspektiv. Den starka utveckling som självstyrelserna har genomgått, samtidigt som man lyckats att finna fredliga lösningar på de konflikter som uppstått, syns viktiga att studera, inte bara i ett nordiskt utan också i ett vidare internationellt perspektiv.Här presenteras konklusionerna från en jämförande studie av de nordiska självstyrelsernas rättsliga, ekonomiska och säkerhetspolitiska utveckling.Den fullständiga studien kan beställas från Ålands fredsinstitut eller laddas ner elektroniskt – www.peace.ax
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- Zhou, X, et al.
(författare)
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Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study
- 2022
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 37:7, s. 701-712
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption (“drinks per week”) and pathological drinking behaviours (“alcohol use disorder” and “problematic alcohol use”), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose–response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10 g/day increase in alcohol consumption. Genetic predisposition to alcohol consumption (“drinks per week”) was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near CDC7 gene, cg10816169 near ZNF318 gene, cg03345232 near RIN3 gene, and cg26312998 near RP11-867G23.13 gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.
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