| 1. |
- Heid, Iris M, et al.
(författare)
-
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
-
Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
|
|
| 2. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
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.
|
|
| 3. |
- Speliotes, Elizabeth K., et al.
(författare)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
| 4. |
- Bejerot, Eva, et al.
(författare)
-
Öppna jämförelser av arbetsmiljö på Internet : Vinster och risker för forskare, respondenter och andra intressenter
- 2011
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- En prototyp för ett rapporteringsverktyg som gör det möjligt för forskare att dela med sig och visualisera data för sina målgrupper via Internet har tagits fram i ett pågående forskningsprojekt. Med detta verktyg kan forskningsresultat baserade på enkätdata redovisas med en hög detaljeringsgrad och användarna kan enkelt jämföra arbetsvillkor för undergrupper: olika arbetsgivare, geografiska områden etcetera. Prototypen som vi skapat kan konceptuellt delas upp i två delar: 1) Ett verktyg som används för att skapa webbplatser för visualisering av stora datamängder. Det är designat för att kunna användas för vitt skilda forskningsprojekt. 2) En webbplats som visualiserar forskningsresultat från en specifik enkätstudie och demonstrerar vad som är möjligt att göra med hjälp av verktyget. Med verktyget presenteras data i form av stapeldiagram och medelvärden direkt på Internet. Designen gör det möjligt att kombinera stora enkätmaterials potential för jämförelser mellan olika undergrupper, arbetsgivare, geografiska områden etcetera. Här kan data re-analyseras och tolkas av dem med kunskap om lokala/regionala förhållanden. Detta gör det möjligt att använda resultaten av större enkätstudier i exempelvis lokalt förbättringsarbete eller i någon form av interaktivt forskningsarbete. Medial uppmärksamhet, särskilt på de platser där resultaten avviker negativt från genomsnittet, kan bidra till ett omvandlingstryck (jfr SKL & Socialstyrelsen 2007). Verktyget programmeras i öppen källkod och blir fritt att använda, reproducera, modifiera och utveckla för envar, enligt principerna i ”open-source”-rörelsen (Stallman 2010). Projektet utvecklas enligt en så kallad ”katedralmodell” (Raymond 1999) där en ”open-source-release” görs när vi arbetat med projektet en tid. Verktyget kommer att följas upp genom att dess för- och nackdelar diskuteras med målgrupp och intressenter. För arbetslivsforskare finns många frågor om vad denna typ av verktyg kan innebära. Vilka vinster respektive problem och risker finns i ”öppna jämförelser av arbetsmiljö”? Hur påverkas viljan att besvara enkäter då en snabbare och mer detaljerad återkoppling är möjlig? Vilka frågor måste ställas kring upphovsrätt då data kan re-analyseras av andra? Hur vi kan designa våra forskningsprojekt för att ta tillvara, eller begränsa, det som informationstekniken möjliggör?
|
|
| 5. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
|
|
| 6. |
- Bähr, Matthias, et al.
(författare)
-
PASSAge - Personalized Mobility, Assistance and Service Systems in an Ageing Society : PASSAge - Personalisierte Mobilität, Assistenz und Service Systeme in einer alternden Gesellschaft
- 2013
-
Ingår i: Lebensqualität im Wandel von Demografie und Technik (AAL 2013). - : VDE-Verlag.
-
Konferensbidrag (refereegranskat)abstract
- The demographic change in modern societies has a significant impact on the future planning of self-determined mobility and mobility means. An optimized accessibility of the means of transportation is required, as well as their connection towards buildings and residences. These connections have to be modular and compatible to the mobility means of the users. Barrier-free accessibility according to the existing norms can address these problems only partially. Broader and holistic concepts are needed here. The project PASSAge aims at the implementation of seamless mobility chains that smoothly connect private, semi-public and public space. Mobility shall be ensured by the extension of existing mobility means with user-oriented components. The project follows the approach to complement the barrier-free access and usage of public transportation with mostly electrically powered compact vehicles and micro vehicles. These have to be adopted by physical means and information technology means to residences and building structures. The goal is to develop a flexible socio-technical infrastructure with a multitude of mobility means and modular building, thus creating synergy effects. Core to this approach is the development of business models, which allow for and ensure the allocation and co-ordination of mobility services. Interfaces will be created for all compact vehicles and micro vehicles that extend their functionality both digitally and physically and thereby enable their ubiquitous connection to the envisioned services.
|
|
| 7. |
|
|
| 8. |
- de Jong, Roelof S., et al.
(författare)
-
4MOST-4-metre Multi-Object Spectroscopic Telescope
- 2014
-
Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 0277-786X .- 1996-756X. ; 9147
-
Konferensbidrag (refereegranskat)abstract
- 4MOST is a wide-field, high-multiplex spectroscopic survey facility under development for the VISTA telescope of the European Southern Observatory (ESO). Its main science drivers are in the fields of galactic archeology, high-energy physics, galaxy evolution and cosmology. 4MOST will in particular provide the spectroscopic complements to the large area surveys coming from space missions like Gaia, eROSITA, Euclid, and PLATO and from ground-based facilities like VISTA, VST, DES, LSST and SKA. The 4MOST baseline concept features a 2.5 degree diameter field-of-view with similar to 2400 fibres in the focal surface that are configured by a fibre positioner based on the tilting spine principle. The fibres feed two types of spectrographs; similar to 1600 fibres go to two spectrographs with resolution R> 5000 (lambda similar to 390-930 nm) and similar to 800 fibres to a spectrograph with R> 18,000 (lambda similar to 392-437 nm & 515-572 nm & 605-675 nm). Both types of spectrographs are fixed-configuration, three-channel spectrographs. 4MOST will have an unique operations concept in which 5 year public surveys from both the consortium and the ESO community will be combined and observed in parallel during each exposure, resulting in more than 25 million spectra of targets spread over a large fraction of the southern sky. The 4MOST Facility Simulator (4FS) was developed to demonstrate the feasibility of this observing concept. 4MOST has been accepted for implementation by ESO with operations expected to start by the end of 2020. This paper provides a top-level overview of the 4MOST facility, while other papers in these proceedings provide more detailed descriptions of the instrument concept[1], the instrument requirements development[2], the systems engineering implementation[3], the instrument model[4], the fibre positioner concepts[5], the fibre feed[6], and the spectrographs[7].
|
|
| 9. |
- Krycka, Kathryn L., et al.
(författare)
-
Resolving Material-Specific Structures within Fe3O4 vertical bar gamma-Mn2O3 Core vertical bar Shell Nanoparticles Using Anomalous Small-Angle X-ray Scattering
- 2013
-
Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 7:2, s. 921-931
-
Tidskriftsartikel (refereegranskat)abstract
- Here it is demonstrated that multiple-energy, anomalous small-angle X-ray scattering (ASAXS) provides significant enhancement in sensitivity to internal material boundaries of layered nanoparticles compared with the traditional modeling of a single scattering energy, even for cases in which high scattering contrast naturally exists. Specifically, the material-specific structure of monodispersed Fe3O4 vertical bar gamma-Mn2O3 core vertical bar shell nanoparticles is determined, and the contribution of each component to the total scattering profile is identified with unprecedented clarity. We show that Fe3O4 vertical bar gamma-Mn2O3 core vertical bar shell nanoparticles with a diameter of 8.2 +/- 0.2 nm consist of a core with a composition near Fe3O4 surrounded by a (MnxFe1-x)(3)O-4 shell with a graded composition, ranging from x approximate to 0.40 at the Inner shell toward x approximate to 0.46 at the surface. Evaluation of the scattering contribution arising from the interference between material-specific layers additionally reveals the presence of Fe3O4 cores without a coating shell. Finally, it is found that the material-specific scattering profile shapes and chemical compositions extracted by this method are independent of the original input chemical compositions used in the analysis, revealing multiple-energy ASAXS as a powerful tool for determining internal nanostructured morphology even if the exact composition of the individual layers is not known a priori.
|
|
| 10. |
- Lambrechts, Marcel M., et al.
(författare)
-
The design of artificial nestboxes for the study of secondary hole-nesting birds: a review of methodological inconsistencies and potential biases
- 2010
-
Ingår i: Acta Ornithologica. - 0001-6454 .- 1734-8471. ; 45:1, s. 1-26
-
Tidskriftsartikel (refereegranskat)abstract
- The widespread use of artificial nestboxes has led to significant advances in our knowledge of the ecology, behaviour and physiology of cavity nesting birds, especially small passerines Nestboxes have made it easier to perform routine monitoring and experimental manipulation of eggs or nestlings, and also repeatedly to capture, identify and manipulate the parents However, when comparing results across study sites the use of nestboxes may also Introduce a potentially significant confounding variable in the form of differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained However, the use of nestboxes may also introduce an unconsidered and potentially significant confounding variable clue to differences in nestbox design amongst studies, such as their physical dimensions, placement height, and the way in which they are constructed and maintained Here we review to what extent the characteristics of artificial nestboxes (e g size, shape, construction material, colour) are documented in the 'methods' sections of publications involving hole-nesting passerine birds using natural or excavated cavities or artificial nestboxes for reproduction and roosting Despite explicit previous recommendations that authors describe in detail the characteristics of the nestboxes used, we found that the description of nestbox characteristics in most recent publications remains poor and insufficient We therefore list the types of descriptive data that should be included in the methods sections of relevant manuscripts and justify this by discussing how variation in nestbox characteristics can affect or confound conclusions from nestbox studies We also propose several recommendations to improve the reliability and usefulness of research based on long-term studies of any secondary hole-nesting species using artificial nestboxes for breeding or roosting.
|
|
| 11. |
- Lazaridis, Iosif, et al.
(författare)
-
Ancient human genomes suggest three ancestral populations for present-day Europeans
- 2014
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 513:7518, s. 409-
-
Tidskriftsartikel (refereegranskat)abstract
- We sequenced the genomes of a similar to 7,000-year-old farmer from Germany and eight similar to 8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes(1-4) with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians(3), who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations' deep relationships and show that early European farmers had similar to 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages.
|
|
