| 1. |
- Lindgren, Cecilia M, et al.
(författare)
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Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.
- 2009
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:6, s. e1000508-
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.
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| 2. |
- Barbary, K., et al.
(författare)
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Discovery of an Unusual Optical Transient with the Hubble Space Telescope
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 690, s. 1358-1362
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Tidskriftsartikel (refereegranskat)abstract
- We present observations of SCP 06F6, an unusual optical transient discovered during the Hubble Space Telescope Cluster Supernova Survey. The transient brightened over a period of ~100 days, reached a peak magnitude of ~ 21.0 in both i 775 and z 850, and then declined over a similar timescale. There is no host galaxy or progenitor star detected at the location of the transient to a 3σ upper limit of i 775 >= 26.4 and z 850 >= 26.1, giving a corresponding lower limit on the flux increase of a factor of ~ 120. Multiple spectra show five broad absorption bands between 4100 Å and 6500 Å, and a mostly featureless continuum longward of 6500 Å. The shape of the light curve is inconsistent with microlensing. The transient's spectrum, in addition to being inconsistent with all known supernova types, does not match any spectrum in the Sloan Digital Sky Survey database. We suggest that the transient may be one of a new class. Based in part on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archive at the Space Telescope Science Institute (STScI). STScI is operated by the Association of Universities for Research in Astronomy (AURA), Inc. under the NASA contract NAS 5-26555. The observations are associated with program GO-10496. Based in part on observations obtained at the European Southern Observatory under ESO program 077.A-0110. Based in part on observations collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan. Some of the data presented herein were obtained at the W.M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California, and NASA.
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| 3. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 4. |
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| 5. |
- Chen, Wei-Min, et al.
(författare)
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Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
- 2008
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; Jun 2, s. 2620-2628
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the genetic variants that regulate fasting glucose concentrations may further our understanding of the pathogenesis of diabetes. We therefore investigated the association of fasting glucose levels with SNPs in 2 genome-wide scans including a total of 5,088 nondiabetic individuals from Finland and Sardinia. We found a significant association between the SNP rs563694 and fasting glucose concentrations (P = 3.5 x 10(-7)). This association was further investigated in an additional 18,436 nondiabetic individuals of mixed European descent from 7 different studies. The combined P value for association in these follow-up samples was 6.9 x 10(-26), and combining results from all studies resulted in an overall P value for association of 6.4 x 10(-33). Across these studies, fasting glucose concentrations increased 0.01-0.16 mM with each copy of the major allele, accounting for approximately 1% of the total variation in fasting glucose. The rs563694 SNP is located between the genes glucose-6-phosphatase catalytic subunit 2 (G6PC2) and ATP-binding cassette, subfamily B (MDR/TAP), member 11 (ABCB11). Our results in combination with data reported in the literature suggest that G6PC2, a glucose-6-phosphatase almost exclusively expressed in pancreatic islet cells, may underlie variation in fasting glucose, though it is possible that ABCB11, which is expressed primarily in liver, may also contribute to such variation.
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| 6. |
- Kathiresan, Sekar, et al.
(författare)
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Common variants at 30 loci contribute to polygenic dyslipidemia
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
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| 7. |
- Björk, Göran, 1956, et al.
(författare)
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Bathymetry and deep-water exchange across the central Lomonosov Ridge at 88°-89°N
- 2007
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Ingår i: Deep-Sea Research I. - : Elsevier BV. ; 54, s. 1197-1208
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Tidskriftsartikel (refereegranskat)abstract
- Seafloor mapping of the central Lomonosov Ridge using a multibeam echo-sounder during the Beringia/Healy–Oden Trans-Arctic Expedition (HOTRAX) 2005 shows that a channel across the ridge has a substantially shallower sill depth than the 2500 m indicated in present bathymetric maps. The multibeam survey along the ridge crest shows a maximum sill depth of about 1870 m. A previously hypothesized exchange of deep water from the Amundsen Basin to the Makarov Basin in this area is not confirmed. On the contrary, evidence of a deep-water flow from the Makarov to the Amundsen Basin was observed, indicating the existence of a new pathway for Canadian Basin Deep Water toward the Atlantic Ocean. Sediment data show extensive current activity along the ridge crest and along the rim of a local Intra Basin within the ridge structure.
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| 8. |
- Cameron, F. J., et al.
(författare)
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Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes?
- 2008
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Ingår i: Diabetic Medicine. - : Wiley-Blackwell Publishing Inc.. - 0742-3071 .- 1464-5491. ; 25:4, s. 463-468
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries.METHODS: Adolescents with Type 1 diabetes aged 11-18 years, from 21 paediatric diabetes care centres, in 19 countries, and their parents were invited to participate. Questionnaires were administered recording demographic data, details of insulin regimens, severe hypoglycaemic events and number of episodes of diabetic ketoacidosis. Adolescents completed the parental involvement scale from the Diabetes Quality of Life for Youth--Short Form (DQOLY-SF) and the Diabetes Family Responsibility Questionnaire (DFRQ). Parents completed the DFRQ and a Parental Burden of Diabetes score. Glycated haemoglobin (HbA(1c)) was analysed centrally on capillary blood.RESULTS: A total of 2062 adolescents completed a questionnaire, with 2036 providing a blood sample; 1994 parents also completed a questionnaire. Family demographic factors that were associated with metabolic outcomes included: parents living together (t = 4.1; P < 0.001), paternal employment status (F = 7.2; d.f. = 3; P < 0.001), parents perceived to be over-involved in diabetes care (r = 0.11; P < 0.001) and adolescent-parent disagreement on responsibility for diabetes care practices (F = 8.46; d.f. = 2; P < 0.001). Although these factors differed between centres, they did not account for centre differences in metabolic outcomes, but were stronger predictors of metabolic control than age, gender or insulin treatment regimen.CONCLUSIONS: Family factors, particularly dynamic and communication factors such as parental over-involvement and adolescent-parent concordance on responsibility for diabetes care appear be important determinants of metabolic outcomes in adolescents with diabetes. However, family dynamic factors do not account for the substantial differences in metabolic outcomes between centres
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| 9. |
- Johnson, B A, et al.
(författare)
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Challenges and opportunities for medications development in alcoholism: An international perspective on collaborations between academia and industry
- 2005
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Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008. ; 29:8, s. 1528-1540
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Tidskriftsartikel (refereegranskat)abstract
- This article represents the proceedings of a symposium presented at the 12th Congress of the International Society for Biomedical Research on Alcoholism held in Heidelberg/Mannheim, Germany, on September 30, 2004. The organizers and cochairs were Bankole A. Johnson, DSc, MD, PhD, and Karl Mann, MD. The presentations included the following: (1) A Perspective from Academia, by Bankole A. Johnson, DSc, MD, PhD; (2) A Perspective from NIAAA, by Mark L. Willenbring, MD; (3) A Perspective from US Clinical Practice, by Robert M. Swift, MD, PhD; (4) A European Perspective on Medications Development, by Otto M. Lesch, MD, PhD, and (5) A Scandinavian Perspective on Evidence-Based Addiction Treatment, by Mats Berglund, MD.
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| 12. |
- Mikhaylushkin, A. S., et al.
(författare)
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Mikhaylushkin et al. Reply
- 2008
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 101:4, s. 049602-
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Rubin, D., et al.
(författare)
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Looking Beyond Lambda with the Union Supernova Compilation
- 2009
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 695, s. 391-403
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Tidskriftsartikel (refereegranskat)abstract
- The recent robust and homogeneous analysis of the world's supernova distance-redshift data, together with cosmic microwave background and baryon acoustic oscillation data—provides a powerful tool for constraining cosmological models. Here we examine particular classes of scalar field, modified gravity, and phenomenological models to assess whether they are consistent with observations even when their behavior deviates from the cosmological constant Λ. Some models have tension with the data, while others survive only by approaching the cosmological constant, and a couple are statistically favored over Λ cold dark matter. Dark energy described by two equation-of-state parameters has considerable phase space to avoid Λ and next-generation data will be required to constrain such physics, with the level of complementarity between probes varying with cosmology.
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