| 1. |
- Evangelou, Evangelos, et al.
(författare)
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Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p = 9.2 x 10(-9)), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
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| 2. |
- Li, Yutang, et al.
(författare)
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The long-awaited synthesis and self-assembly of a small rigid C3-symmetric trilactam
- 2022
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Ingår i: Chemical Communications. - 1359-7345. ; 58:23, s. 3751-3754
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Tidskriftsartikel (refereegranskat)abstract
- The challenging synthesis of a fused C3-symmetric trilactam (1) was executed in racemic and enantiomerically pure form. The rigidity, symmetry and high density of hydrogen bonding motifs make 1 an attractive candidate for self-assembly study, which revealed different hydrogen bond patterns in the crystals of rac-1-d3 and (+)-(SSS)-1.
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| 3. |
- Scott, Robert A, et al.
(författare)
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No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels
- 2012
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Ingår i: Diabetes. - Alexandria, VA : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 61:5, s. 1291-1296
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Tidskriftsartikel (refereegranskat)abstract
- Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.
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| 4. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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| 5. |
- Thorgeirsson, Thorgeir E, et al.
(författare)
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A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7187, s. 9-638
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
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| 6. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 7. |
- Abdallah, J., et al.
(författare)
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A determination of the centre-of-mass energy at LEP2 using radiative two-fermion events
- 2006
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 46:2, s. 295-305
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Tidskriftsartikel (refereegranskat)abstract
- Using e(+)e(-) -> mu(+)mu(-)(gamma) and e(+)e(-) -> q (q) over bar(gamma) events radiative to the Z pole, DELPHI has determined the centre-of-mass energy, root s, using energy and momentum constraint methods. The results are expressed as deviations from the nominal LEP centre-of-mass energy, measured using other techniques. The results are found to be compatible with the LEP Energy Working Group estimates for a combination of the 1997 to 2000 data sets.
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| 8. |
- Abdallah, J, et al.
(författare)
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A measurement of the branching fractions of the b-quark into charged and neutral b-hadrons
- 2003
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 576:1-2, s. 29-42
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Tidskriftsartikel (refereegranskat)abstract
- The production fractions of charged and neutral b-hadrons in b-quark events from Z(0) decays have been measured with the DELPHI detector at LEP. An algorithm has been developed, based on a neural network, to estimate the charge of the weakly-decaying b-hadron by distinguishing its decay products from particles produced at the primary vertex. From the data taken in the years 1994 and 1995, the fraction of (b) over bar -quarks fragmenting into positively charged weakly-decaying b-hadrons has been measured to be: f(+) = (42.09+/-0.82(stat)+/-0.89(syst))%. Subtracting the rates for charged Xi(b)(+) and Omega(b)(+) baryons gives the production fraction of B+ mesons: f(Bu) = (40.99+/-0.82(stat)+/-1.11 (syst)) %.
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| 9. |
- Abdallah, J., et al.
(författare)
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A measurement of the tau hadronic branching ratios
- 2006
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 46:1, s. 1-26
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Tidskriftsartikel (refereegranskat)abstract
- The exclusive and semi-exclusive branching ratios of the tau lepton hadronic decay modes (h(-)upsilon(tau), h(-)pi(0)upsilon(tau), h(-)pi(0)pi(0)upsilon(tau), h(-) >= 2 pi(0)nu(tau), 2h(-)h(+)upsilon(tau), 2h(-)h(+)>= 2 pi(0)upsilon(tau), 3h(-)2h(+)upsilon(tau) and 3h(-)2h(+) >= 1 pi(0)upsilon(tau)) were measured with data from the DELPHI detector at LEP.
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| 10. |
- Abdallah, J, et al.
(författare)
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A precise measurement of the B+, B-0 and mean b-hadron lifetime with the DELPHI detector at LEP I
- 2004
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 33:3, s. 307-324
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Tidskriftsartikel (refereegranskat)abstract
- Final results from the DELPHI Collaboration on the lifetime of B+ and B-0 mesons and the mean b-hadron lifetime, are presented using the data collected at the Z(0) peak in 1994 and 1995. Elaborate, inclusive, secondary vertexing methods have been employed to ensure a b-hadron reconstruction with good efficiency. To separate samples of B+ and B-0 mesons, high performance neural network techniques are used that achieve very high purity signals. The results obtained are: tau(B+) = 1.624+/-0.014 (stat)+/-0.018 (syst) ps tau(B)0 = 1.531+/-0.021 (stat)+/-0.031 (syst) ps tau(B+)/tau(B)0 = 1.060+/-0.021 (stat)+/-0.024 (syst) and for the average b-hadron lifetime: taub/tau(B)0 = 1.570+/-0.005 (stat)+/-0.008 (syst) ps.
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