| 11. |
- Saxena, Richa, et al.
(författare)
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Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:2, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958–30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, β (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 × 10−15). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 × 10−17; ratio of insulin to glucose area under the curve, P = 1.3 × 10−16) and diminished incretin effect (n = 804; P = 4.3 × 10−4). We also identified variants at ADCY5 (rs2877716, P = 4.2 × 10−16), VPS13C (rs17271305, P = 4.1 × 10−8), GCKR (rs1260326, P = 7.1 × 10−11) and TCF7L2 (rs7903146, P = 4.2 × 10−10) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09–1.15, P = 4.8 × 10−18).
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| 12. |
- Birkby, J. L., et al.
(författare)
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WTS-2 b: a hot Jupiter orbiting near its tidal destruction radius around a K dwarf
- 2014
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 440:2, s. 1470-1489
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of WTS-2 b, an unusually close-in 1.02-d hot Jupiter (M-P = 1.12M(J), R-P = 1.30R(J)) orbiting a K2V star, which has a possible gravitationally bound M-dwarf companion at 0.6 arcsec separation contributing similar to 20 per cent of the total flux in the observed J-band light curve. The planet is only 1.5 times the separation from its host star at which it would be destroyed by Roche lobe overflow, and has a predicted remaining lifetime of just similar to 40 Myr, assuming a tidal dissipation quality factor of Q(*)' = 10(6).Q(*)' is a key factor in determining how frictional processes within a host star affect the orbital evolution of its companion giant planets, but it is currently poorly constrained by observations. We calculate that the orbital decay of WTS-2 b would correspond to a shift in its transit arrival time of T-shift similar to 17 s after 15 yr assuming Q(*)' = 10(6). A shift less than this would place a direct observational constraint on the lower limit of Q(*)' in this system. We also report a correction to the previously published expected T-shift for WASP-18 b, finding that T-shift = 356 s after 10 yr for Q(*)' = 10(6), which is much larger than the estimated 28 s quoted in WASP-18 b discovery paper. We attempted to constrain Q(*)' via a study of the entire population of known transiting hot Jupiters, but our results were inconclusive, requiring a more detailed treatment of transit survey sensitivities at long periods. We conclude that the most informative and straightforward constraints on Q(*)' will be obtained by direct observational measurements of the shift in transit arrival times in individual hot Jupiter systems. We show that this is achievable across the mass spectrum of exoplanet host stars within a decade, and will directly probe the effects of stellar interior structure on tidal dissipation.
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| 13. |
- Hense, S, et al.
(författare)
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Determinants of Attrition to Follow-Up in a Multicentre Cohort
- 2013
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Ingår i: Epidemiology Research International. - : Hindawi Limited. - 2090-2972 .- 2090-2980.
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Tidskriftsartikel (refereegranskat)abstract
- Cohort participant retention is a crucial element and may depend on several factors. Based on data from a multicentre cohort of European children, the effect of baseline participation on attrition and the association with and the impact of single determinants in relation to the extent of attrition were investigated. Data was available for 16,225 children from the IDEFICS baseline survey (2007/2008). Attrition was defined as nonparticipation in the first follow-up examination (2009/2010). Determinants of attrition were analysed by logistic regression. The statistical significance level was set at to account for the large sample size. The strongest associations were seen for baseline item non-response, especially when information on migration background (odds ratio (OR) = 1.55; 99% confidence interval (CI): 1.04, 2.31), single parenthood (OR = 1.37; 99% CI: 1.12, 1.67), or well-being (OR = 1.46; 99% CI: 1.19, 1.79) was lacking. Drop-out proportion rose with the number of missing items. Overweight, low education, single parenthood and low well-being scores were independent determinants of attrition. Baseline participation, and the individual determinant effects seemed unrelated to the variation of the extent of attrition between study centres. A high level of item nonresponse as well as overweight and disadvantageous sociodemographic conditions were identified as main attrition determinants, suggesting the consideration of these aspects in conduct and analysis of cohort studies in childhood obesity research.
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| 14. |
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| 15. |
- Ingelsson, Erik, et al.
(författare)
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Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans
- 2010
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Konferensbidrag (refereegranskat)abstract
- OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS-The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS-Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. Diabetes 59:1266-1275, 2010
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| 16. |
- Ingelsson, Erik, et al.
(författare)
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Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
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| 17. |
- Schoch, CL, et al.
(författare)
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Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:16, s. 6241-6246
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Tidskriftsartikel (refereegranskat)abstract
- Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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| 18. |
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| 19. |
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| 20. |
- Borrell, C, et al.
(författare)
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Socioeconomic inequalities in mortality in 16 European cities
- 2014
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 42:3, s. 245-254
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To explore inequalities in total mortality between small areas of 16 European cities for men and women, as well as to analyse the relationship between these geographical inequalities and their socioeconomic indicators. Methods: A cross-sectional ecological design was used to analyse small areas in 16 European cities (26,229,104 inhabitants). Most cities had mortality data for a period between 2000 and 2008 and population size data for the same period. Socioeconomic indicators included an index of socioeconomic deprivation, unemployment, and educational level. We estimated standardised mortality ratios and controlled for their variability using Bayesian models. We estimated relative risk of mortality and excess number of deaths according to socioeconomic indicators. Results: We observed a consistent pattern of inequality in mortality in almost all cities, with mortality increasing in parallel with socioeconomic deprivation. Socioeconomic inequalities in mortality were more pronounced for men than women, and relative inequalities were greater in Eastern and Northern European cities, and lower in some Western (men) and Southern (women) European cities. The pattern of excess number of deaths was slightly different, with greater inequality in some Western and Northern European cities and also in Budapest, and lower among women in Madrid and Barcelona. Conclusions: In this study, we report a consistent pattern of socioeconomic inequalities in mortality in 16 European cities. Future studies should further explore specific causes of death, in order to determine whether the general pattern observed is consistent for each cause of death.
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