| 1. |
- Locke, Adam E, et al.
(author)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 2. |
- Turcot, Valerie, et al.
(author)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 3. |
- Lango Allen, Hana, et al.
(author)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Journal article (peer-reviewed)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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| 4. |
- Elks, Cathy E, et al.
(author)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Journal article (peer-reviewed)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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| 5. |
- Ballesteros, S., et al.
(author)
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The role of ICT and networking in healthy ageing
- 2012
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In: Proceedings of the 5th International Conference on PErvasive Technologies Related to Assistive Environments. - New York, NY, USA : ACM Digital Library. - 9781450313001
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Conference paper (peer-reviewed)abstract
- In this paper, we report the results from the psychologicalassessment conducted using a test battery composed of cognitiveand social wellbeing tests and questionnaires performed by usersand controls that participated in the AGNES project in Spain,Sweden and Greece at the beginning of the study and after thedeployment of the first prototype. The project carries out noveltechnological interventions in an emerging area in ageingresearch. The main innovation is the integration of differenttechnological components and social networking to provide anovel solution to the ageing population living at home. Themotivation was based on relevant findings on the psychology ofageing and the need for technologies to support the ageingpopulation. End-users have been heavily involved, providingdesign input, continuum evaluation and feedback. Theprojectfocuses on improving the mental and physical wellbeing ofelderly people living at home, who often suffer the effects ofsocial and physical isolation including cognitive decline, lowactivity levels and poor mood states. The main results were thatthe users but not the control participants improved cognitiveperformance andthe feeling of being treated with respect, beingindependent, self-realization and greater achievement.
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| 6. |
- Waterworth, John A., et al.
(author)
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Presence in the Future
- 2008. - 1
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In: Presence 2008. - Padova : HT Lab, University of Padova. - 9788861292871 ; , s. 61-65
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Conference paper (other academic/artistic)abstract
- We view the sense of presence as being the result of an evolved neuropsychological process, created through the evolution of the central nervous system, and which solves a key problem for an organism’s survival: how to differentiate between the internal (the self) and the external (the other). When we experience strong mediated presence, our experience is that the technology has become part of the self, and the mediated reality part of the other. There is no attentional effort of access to information. We can perceive and often act directly, as if unmediated. The rapidly developing phenomena of mediated presence point beyond the replacement of the world with virtual other worlds, and towards dynamically changing relationships between self (and selves) and others. We discuss the implications these developments for the future of the sense of presence and of presence research.
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| 7. |
- Waterworth, John, et al.
(author)
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Presence as a Dimension of Communication : Context of Use and the Person
- 2006
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In: From Communication to Presence. - Amsterdam : IOS Press. - 9781586036621 ; , s. 80-95
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Book chapter (peer-reviewed)abstract
- We claim that presence is elicited most strongly when information is presented as an inhabitable, external world. Technical developments that permit this, such as the creation of interactive, immersive virtual environments herald a profound change in how people relate to sources of information, and how they communicate. This change has psychological, social and cultural effects. It has been claimed that in many ways, our relationship to information becomes that of our ancestral, pre-literate relationship to the physical world. By this view, we are heading for a post-literate future of body-based communication. But this view is too simple, since information must serve a variety of purposes, and how much presence is desirable in a communicative situation depends on many factors, including the communication devices available, the intended use and the context of use. In addition, differences between individuals, such as personality, as well as physical and psychological state, will affect how readily presence is invoked and also its impact on the individual concerned. In this chapter, we expand on the general notion of presence as a dimension of communication, and how this perspective can inform an understanding of designed variations in presence as a function of use, context, and individual psychological factors.
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| 8. |
- MacFarlane, Anne, et al.
(author)
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The e-health implementation toolkit : qualitative evaluation across four European countries
- 2011
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In: Implementation Science. - : BioMed Central. - 1748-5908. ; 06:122
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Journal article (peer-reviewed)abstract
- Background: Implementation researchers have attempted to overcome the research-practice gap in e-health by developing tools that summarize and synthesize research evidence of factors that impede or facilitate implementation of innovation in healthcare settings. The e-Health Implementation Toolkit (e-HIT) is an example of such a tool that was designed within the context of the United Kingdom National Health Service to promote implementation of e-health services. Its utility in international settings is unknown. Methods: We conducted a qualitative evaluation of the e-HIT in use across four countries--Finland, Norway, Scotland, and Sweden. Data were generated using a combination of interview approaches (n = 22) to document e-HIT users' experiences of the tool to guide decision making about the selection of e-health pilot services and to monitor their progress over time. Results: e-HIT users evaluated the tool positively in terms of its scope to organize and enhance their critical thinking about their implementation work and, importantly, to facilitate discussion between those involved in that work. It was easy to use in either its paper- or web-based format, and its visual elements were positively received. There were some minor criticisms of the e-HIT with some suggestions for content changes and comments about its design as a generic tool (rather than specific to sites and e-health services). However, overall, e-HIT users considered it to be a highly workable tool that they found useful, which they would use again, and which they would recommend to other e-health implementers. Conclusion: The use of the e-HIT is feasible and acceptable in a range of international contexts by a range of professionals for a range of different e-health systems.
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