| 1. |
- Arking, D. E., et al.
(författare)
-
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
-
Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
|
|
| 2. |
- Furberg, Helena, et al.
(författare)
-
Genome-wide meta-analyses identify multiple loci associated with smoking behavior
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
-
Tidskriftsartikel (refereegranskat)abstract
- Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
|
|
| 3. |
- McKay, James D., et al.
(författare)
-
A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
|
|
| 4. |
|
|
| 5. |
- Urayama, Kevin Y., et al.
(författare)
-
Genome-Wide Association Study of Classical Hodgkin Lymphoma and Epstein-Barr Virus Status-Defined Subgroups
- 2012
-
Ingår i: Journal of the National Cancer Institute. - Oxford : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 104:3, s. 240-253
-
Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification. We conducted a genome-wide association study of 1200 cHL patients and 6417 control subjects, with validation in an independent replication series, to identify common genetic variants associated with total cHL and subtypes defined by tumor EBV status. Multiple logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) assuming a log-additive genetic model for the variants. All statistical tests were two-sided. Two novel loci associated with total cHL irrespective of EBV status were identified in the major histocompatibility complex region; one resides adjacent to MICB (rs2248462: OR = 0.61, 95% CI = 0.53 to 0.69, P = 1.3 x 10(-13)) and the other at HLA-DRA (rs2395185: OR = 0.56, 95% CI = 0.50 to 0.62, P = 8.3 x 10(-25)) with both results confirmed in an independent replication series. Consistent with previous reports, associations were found between EBV-positive cHL and genetic variants within the class I region (rs2734986, HLA-A: OR = 2.45, 95% CI = 2.00 to 3.00, P = 1.2 x 10(-15); rs6904029, HCG9: OR = 0.46, 95% CI = 0.36 to 0.59, P = 5.5 x 10(-10)) and between EBV-negative cHL and rs6903608 within the class II region (rs6903608, HLA-DRA: OR = 2.08, 95% CI = 1.84 to 2.35, P = 6.1 x 10(-31)). The association between rs6903608 and EBV-negative cHL was confined to the nodular sclerosis histological subtype. Evidence for an association between EBV-negative cHL and rs20541 (5q31, IL13: OR = 1.53, 95% CI = 1.32 to 1.76, P = 5.4 x 10(-9)), a variant previously linked to psoriasis and asthma, was observed; however, the evidence for replication was less clear. Notably, one additional psoriasis-associated variant, rs27524 (5q15, ERAP1), showed evidence of an association with cHL in the genome-wide association study (OR = 1.21, 95% CI = 1.10 to 1.33, P = 1.5 x 10(-4)) and replication series (P = .03). Overall, these results provide strong evidence that EBV status is an etiologically important classification of cHL and also suggest that some components of the pathological process are common to both EBV-positive and EBV-negative patients.
|
|
| 6. |
|
|
| 7. |
- Shah, F. U., et al.
(författare)
-
Halogen-free chelated orthoborate ionic liquids and organic ionic plastic crystals
- 2012
-
Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 22:14, s. 6928-6938
-
Tidskriftsartikel (refereegranskat)abstract
- Five halogen-free orthoborate salts comprised of three different cations (cholinium, pyrrolidinium and imidazolium) and two orthoborate anions, bis(mandelato) borate and bis(salicylato) borate, were synthesised and characterised by DSC, X-ray diffraction and NMR. DSC measurements revealed that glass transition points of these orthoborate salts are in the temperature range from -18 to -2 degrees C. In addition, it was found that [EMPy][BScB] and [EMIm][BScB] salts have solid-solid phase transitions below their melting points, i.e. they exhibit typical features of plastic crystals. Salts of the bis(salicylato) borate anion [BScB](-) have higher melting points compared with corresponding salts of the bis(mandelato) borate anion [BMB](-). Single crystal X-ray diffraction crystallography (for [Chol][BScB] crystals) and solid-state multinuclear (C-13, B-11 and N-15) NMR spectroscopy were employed for the structural characterisation of [Chol][BScB], [EMPy][BScB] and [EMIm][BScB], which are solids at room temperature: a strong interaction between [BScB](-) anions and [Chol](+) cations was identified as (i) hydrogen bonding between OH of [Chol](+) and carbonyl groups of [BScB](-) and (ii) as the inductive C-H center dot center dot center dot pi interaction. In the other salt, [EMIm][BScB], anions exhibit pi center dot center dot center dot pi stacking in combination with C-H center dot center dot center dot pi interactions with [EMIm]+ cations. These interactions were not identified in [EMPy] [BScB] probably because of the lack of aromaticity in cations of the latter system. Our data on the formation of a lanthanum complex with bis(salicylato) borate in the liquid mixture of La3+(aq) with [Chol][BScB] suggest that this class of novel ILs can be potentially used in the extraction processes of metal ions of rare earth elements.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Looi, Jeffrey C. L., et al.
(författare)
-
The Australian, US, Scandinavian Imaging Exchange (AUSSIE): an innovative, virtually-integrated health research network embedded in health care
- 2014
-
Ingår i: Australasian Psychiatry. - : SAGE Publications. - 1039-8562 .- 1440-1665. ; 22:3, s. 260-265
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe the development, design and function of an innovative international clinical research network for neuroimaging research, based in Australia, within a joint state health service/medical school. This Australian, US, Scandinavian Imaging Exchange (AUSSIE) network focuses upon identifying neuroimaging biomarkers for neuropsychiatric and neurodegenerative disease. Methods: We describe a case study of the iterative development of the network, identifying characteristic features and methods which may serve as potential models for virtual clinical research networks. This network was established to analyse clinically-derived neuroimaging data relevant to neuropsychiatric and neurodegenerative disease, specifically in relation to subcortical brain structures. Results: The AUSSIE network has harnessed synergies from the individual expertise of the component groups, primarily clinical neuroscience researchers, to analyse a variety of clinical data. Conclusion: AUSSIE is an active virtual clinical research network, analogous to a connectome, which is embedded in health care and has produced significant research, advancing our understanding of neuropsychiatric and neurodegenerative disease through the lens of neuroimaging.
|
|
| 13. |
- Looi, JCL, et al.
(författare)
-
Frontotemporal dementia as a frontostriatal disorder: neostriatal morphology as a biomarker and structural basis for an endophenotype
- 2012
-
Ingår i: The Australian and New Zealand journal of psychiatry. - : SAGE Publications. - 1440-1614 .- 0004-8674. ; 46:5, s. 422-434
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: This article reviews the evidence for a re-conceptualisation of a subtype of frontotemporal lobar degeneration (FTLD), frontotemporal dementia (FTD), as a frontostriatal disorder, working towards an endophenotype. Method: We provide an overview of the role of frontostriatal circuits relevant to FTLD and FTD, as a subset of larger-scale distributed brain networks. We discuss the role of a strategic structure in these circuits, the neostriatum. Then we review the relationship of the clinical features of FTLD to frontostriatal circuits, correlating this with neuropsychological and neuropathological data. Conclusion: The unique structure and linkages of the neostriatum make it an ideal structure for in vivo neuroimaging to understand the neuroanatomical basis of FTD. We develop a frontostriatal endophenotypic model for FTD as a platform for further investigation.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Nordström, Jonas, 1980, et al.
(författare)
-
Aggregation, ageing and transport properties of surface modified fumed silica dispersions
- 2010
-
Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 6:10, s. 2293-2299
-
Tidskriftsartikel (refereegranskat)abstract
- We have investigated the aggregation, ageing and transport properties of surface modified silica dispersions in DMSO by photon correlation spectroscopy and conductivity measurements. The surface modification introduces Li+-ions that dissociate in the dispersion creating a single Li+-ion conducting electrolyte. We show that the surface modification changes the aggregation and ageing properties of the material. There is a pronounced ageing observed for the modified silica dispersions. At high concentrations of fumed silica a gel state is found, which in the case of the surface modified silica is a very weak gel that can be rejuvenated by ultrasonic treatment. The key parameter controlling the aggregation in this system is hydrogen bonding and the surface modification results in a very low number of sites for hydrogen bonding. In addition there is a contribution from repulsive electrostatic interactions in the surface modified silica dispersions due to the highly charged surfaces of these particles. Furthermore, the Li+-ion diffusion, at low silica concentration, is three orders of magnitude faster than that of the silica particles and in the gel state the silica particles are immobile. We also find that the Li+-ion diffusion is virtually independent of the silica concentration in the dispersions.
|
|
| 18. |
- Shah, Faiz Ullah, et al.
(författare)
-
Halogen-free chelated orthoborate ionic liquids and organic ionic plastic crystals
- 2012
-
Ingår i: Journal of Materials Chemistry. - 0959-9428 .- 1364-5501. ; 22:14, s. 6928-6938
-
Tidskriftsartikel (refereegranskat)abstract
- Five halogen-free orthoborate salts comprised of three different cations (cholinium, pyrrolidinium and imidazolium) and two orthoborate anions, bis(mandelato)borate and bis(salicylato)borate, were synthesised and characterised by DSC, X-ray diffraction and NMR. DSC measurements revealed that glass transition points of these orthoborate salts are in the temperature range from −18 to −2 °C. In addition, it was found that [EMPy][BScB] and [EMIm][BScB] salts have solid–solid phase transitions below their melting points, i.e. they exhibit typical features of plastic crystals. Salts of the bis(salicylato)borate anion [BScB]− have higher melting points compared with corresponding salts of the bis(mandelato)borate anion [BMB]−. Single crystal X-ray diffraction crystallography (for [Chol][BScB] crystals) and solid-state multinuclear (13C, 11B and 15N) NMR spectroscopy were employed for the structural characterisation of [Chol][BScB], [EMPy][BScB] and [EMIm][BScB], which are solids at room temperature: a strong interaction between [BScB]− anions and [Chol]+ cations was identified as (i) hydrogen bonding between OH of [Chol]+ and carbonyl groups of [BScB]− and (ii) as the inductive C–Hπ interaction. In the other salt, [EMIm][BScB], anions exhibit ππ stacking in combination with C–Hπ interactions with [EMIm]+ cations. These interactions were not identified in [EMPy][BScB] probably because of the lack of aromaticity in cations of the latter system. Our data on the formation of a lanthanum complex with bis(salicylato)borate in the liquid mixture of La3+(aq) with [Chol][BScB] suggest that this class of novel ILs can be potentially used in the extraction processes of metal ions of rare earth elements.
|
|
| 19. |
- Tajar, Abdelouahid, et al.
(författare)
-
Elevated levels of gonadotrophins but not sex steroids are associated with musculoskeletal pain in middle-aged and older European men
- 2011
-
Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 152:7, s. 1495-1501
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine the association of hormone levels with the occurrence of musculoskeletal pain. Men ages 40 to 79 years were recruited from population registers in 8 European centres. Subjects were asked to complete a postal questionnaire, which enquired about lifestyle and the occurrence of musculoskeletal pain over the past month. Total testosterone (T), oestradiol (E2), luteinising hormone (LH), and follicle-stimulating hormone (FSH) were assayed from a fasting blood sample. The association between pain status and hormone levels was assessed using multinomial logistic regression with results expressed as relative risk ratios (RRR) and 95% confidence intervals (CI). A total of 3206 men had complete data on pain status. Of these, 8.7% reported chronic widespread pain (CWP), whereas 50% had some pain although not CWP and were classified as having some pain. T and E2 were not associated with musculoskeletal pain, whereas significant differences in LH and FSH levels were found between pain groups. After adjustment for age and other possible confounders, the association between pain status and both LH and FSH persisted. Compared with those in the lowest tertile of LH, those in the highest tertile were more likely to report some pain (vs no pain, RRR = 1.28; 95% CI 1.09 to 1.50) and also CWP (vs no pain, RRR = 1.51; 95% CI 1.10 to 2.07). Similar results were found for FSH. Gonadotrophins, but not sex steroid hormone levels, are associated with musculoskeletal pain in men. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
|
|
