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| 65. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 66. |
- Lissner, Lauren, 1956, et al.
(författare)
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Statement by Members of the Task Force on Prevention and Public Health of the European Association for the Study of Obesity (EASO)
- 2009
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Ingår i: Obesity Facts. - 1662-4025. ; 2:1, s. 54-55
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Tidskriftsartikel (refereegranskat)abstract
- This document is signed by all members of the task force, who will contribute knowledge on the problem of obesity in the various regions of Europe. It is apparent from the wide range of available prevalence estimates that the magnitude of the obesity epidemic varies across Europe. However certain similarities are present, including consistent but varying increases in prevalence in all countries from the end of the 20th century to the present, together with clear inverse socioeconomic gradients. The lack of harmonized surveillance efforts across Europe makes international monitoring and comparative assessments imprecise at best. A particularly worrisome aspect of this epidemic is the recently observed increase in the proportion of European children with overweight and obesity. The Task Force is in agreement that the epidemic reflects changing lifestyles and environments and that prevention can only be achieved by identifying and arresting these trends, a statement that has been repeated by many groups advocating obesity prevention over the years. For instance, in 1999 the Milan Declaration was made on behalf of all members of the EASO, resolving to support the development of coherent national and Europe-wide strategies for the prevention and management of overweight and obesity. Since then, there have been recent steps to develop a public health strategy for obesity prevention across Europe, including most notably the 2006 European Ministerial Conference on Counteracting Obesity in the European Region. At that time, all member states of WHO Europe met in Istanbul and explicitly agreed on an ecological approach to fighting the obesity epidemic, with a charter recognizing that counteracting obesity requires a multidisciplinary effort with a timeline for improvements (www.euro.who.int/ document/E89567.pdf). In this context, the vision of our Task Force is to provide guidance and leadership to researchers, governments, and agencies that are trying to fulfill the charter developed in Istanbul and other recent initiatives. Specifically, we will support and strengthen research and interventions to improve prevention of obesity across Europe, within the framework of the EASO.
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| 67. |
- Mohr, C., et al.
(författare)
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Ambient observations of dimers from terpene oxidation in the gas phase: Implications for new particle formation and growth
- 2017
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Ingår i: Geophysical Research Letters. - 0094-8276. ; 44:6, s. 2958-2966
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Tidskriftsartikel (refereegranskat)abstract
- We present ambient observations of dimeric monoterpene oxidation products (C16-20HyO6-9) in gas and particle phases in the boreal forest in Finland in spring 2013 and 2014, detected with a chemical ionization mass spectrometer with a filter inlet for gases and aerosols employing acetate and iodide as reagent ions. These are among the first online dual-phase observations of such dimers in the atmosphere. Estimated saturation concentrations of 10(-15) to 10(-6)mu gm(-3) (based on observed thermal desorptions and group-contribution methods) and measured gas-phase concentrations of 10(-3) to 10(-2)mu gm(-3) (similar to 10(6)-10(7)moleculescm(-3)) corroborate a gas-phase formation mechanism. Regular new particle formation (NPF) events allowed insights into the potential role dimers may play for atmospheric NPF and growth. The observationally constrained Model for Acid-Base chemistry in NAnoparticle Growth indicates a contribution of similar to 5% to early stage particle growth from the similar to 60 gaseous dimer compounds. Plain Language Summary Atmospheric aerosol particles influence climate and air quality. We present new insights into how emissions of volatile organic compounds from trees are transformed in the atmosphere to contribute to the formation and growth of aerosol particles. We detected for the first time over a forest, a group of organic molecules, known to grow particles, in the gas phase at levels far higher than expected. Previous measurements had only measured them in the particles. This finding provides guidance on how models of aerosol formation and growth should describe their appearance and fate in the atmosphere.
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| 68. |
- Nettleton, Jennifer A, et al.
(författare)
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Gene x dietary pattern interactions in obesity : analysis of up to 68 317 adults of European ancestry
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 24:16, s. 4728-4738
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is highly heritable. Genetic variants showing robust associationswith obesity traits have been identified through genome wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphismswere genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjustedWHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006-0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjustedWHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance.
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| 69. |
- Nyandoro, Stephen S., 1975, et al.
(författare)
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Flavonoids from Erythrina schliebenii
- 2017
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 80:2, s. 377-383
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Tidskriftsartikel (refereegranskat)abstract
- Prenylated and O-methylflavonoids including one new pterocarpan (1), three new isoflavones (2-4), and nineteen known natural products (5-23) were isolated and identified from the root, stem bark, and leaf extracts of Erythrina schliebenii. The crude extracts and their constituents were evaluated for antitubercular activity against Mycobacterium tuberculosis (H37Rv strain), showing MICs of 32-64 mu g mL(-1) and 36.9-101.8 mu M, respectively. Evaluation of their toxicity against the aggressive human breast cancer cell line MDA-MB-231 indicated EC50 values of 13.0-290.6 mu M (pure compounds) and 38.3 to >100 mu g mL(-1) (crude extracts). RAMSON D, 1973, PHYTOCHEMISTRY, V12, P2211
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| 70. |
- Orava, J., et al.
(författare)
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Blunted Metabolic Responses to Cold and Insulin Stimulation in Brown Adipose Tissue of Obese Humans
- 2013
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 21:11, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Inactive brown adipose tissue (BAT) may predispose to weight gain. This study was designed to measure metabolism in the BAT of obese humans, and to compare it to that in lean subjects. The impact of weight loss on BAT and the association of detectable BAT with various metabolic characteristics were also assessed. Design and Methods: Using positron emission tomography (PET), cold-and insulin-stimulated glucose uptake and blood flow in the BAT of obese and lean humans were quantified. Further, cold-induced glucose uptake was measured in obese subjects before and after a 5-month conventional weight loss. Results: Mean responses in BAT glucose uptake rate to both cold and insulin stimulation were twice as large in lean as in obese subjects. Blood flow in BAT was also lower in obese subjects under cold conditions. The increase in cold-induced BAT glucose uptake rate after weight loss was not statistically significant. Subjects with cold-activated detectable BAT were leaner and had higher whole-body insulin sensitivity than BAT-negative subjects, irrespective of age and gender. Conclusions: The effects of cold and insulin on BAT activity are severely blunted in obesity, and the presence of detectable BAT may contribute to a metabolically healthy status.
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