| 1. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Yang, Jian, et al.
(författare)
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FTO genotype is associated with phenotypic variability of body mass index
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
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Tidskriftsartikel (refereegranskat)abstract
- There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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| 4. |
- Loos, Ruth J. F., et al.
(författare)
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Common variants near MC4R are associated with fat mass, weight and risk of obesity
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:6, s. 768-775
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Tidskriftsartikel (refereegranskat)abstract
- To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.
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| 5. |
- Daly, Robert J., et al.
(författare)
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A palynological study of an extinct arctic ecosystem from the Palaeocene of Northern Alaska
- 2011
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Ingår i: Review of Palaeobotany and Palynology. - : Elsevier BV. - 0034-6667. ; 166:1-2, s. 107-116
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Tidskriftsartikel (refereegranskat)abstract
- The Palaeocene arctic supported a vegetation type quite distinct from the tundra and polar desert of today. Here we demonstrate, through the palynological record, the structure of this extinct vegetation and its dynamics over this period. The Late Palaeocene coal-bearing units of the Sagwon Bluffs on Alaska's North Slope (present latitude 69 degrees N) are predominantly fine-grained, non-marine and rich in palynomorph-bearing sediments. From the analysed palynological assemblage we were able to demonstrate, using 'Detrended Correspondence Analysis' (DCA) and 'Fuzzy c-Means Cluster Analysis' (FCM), 1) a complex heterogeneous ecosystem, 2) its major successional states, and 3) its development over an extended period. The climax state of the floodplain was dominated by flood-tolerant, deciduous conifers such as Metasequoia. A more heterogeneous mid-successional assemblage is represented by angiosperm and gymnosperm co-dominance with an angiosperm dominance of Corylus, while early-successional ecological groups, dominated by ferns and bryophytes, are considered to represent riparian and post-disturbance niches. The structure of this vegetation does not remain static over the course of the stratigraphic interval represented. We observe a particularly dramatic ecological change for instance, following the deposition of a large conglomeratic unit. It is hypothesized that this corresponds to altered drainage and/or precipitation on the North Slope. The vegetation examined herein shows marked similarities to that of other palaeobotanical studies from various sites of similar age at high northern latitudes. It is hence considered to represent an extensive and long-lived circumpolar arctic biome. (C) 2011 Elsevier B.V. All rights reserved.
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| 6. |
- de Mauleon, Adelaide, et al.
(författare)
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Associated Factors With Antipsychotic Use in Long-Term Institutional Care in Eight European Countries: Results From the RightTimePlaceCare Study
- 2014
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Ingår i: Journal of the American Medical Directors Association. - Philadelphia : Elsevier. - 1525-8610 .- 1538-9375. ; 15:11, s. 812-818
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine factors associated with the antipsychotic (AP) prescription for people with dementia (PwD) recently admitted to institutional long-term carefacilities (LTCFs) and to ascertain differences in the use of this medication in 8 European countries.Design: An exploratory cross-sectional study.Setting: LTCFs from 8 European countries (Estonia, Finland, France, Germany, The Netherlands, Spain, Sweden, and England).Participants: A total of 791 PwD recently admitted to an LTCF and their caregivers.Measurements: Baseline data from RightTimePlaceCare survey was used. Patients' medical conditions, neuropsychiatric symptoms, physical and cognitive status, and medications were recorded. Multiple logistic regression models were used to assess associations with the AP use. Results: A group of 296 patients (37.4%) of 791 patients recently admitted received AP medication. The prevalence of the use of 1 or more APs varied between study countries, ranging from 12% in Sweden to 54% inSpain. Factors independently associated with the AP use were living in Sweden [odds ratio (OR) 0.12, 95% confidence interval (CI) 0.05-0.30], Finland (OR 0.26, 95% CI 0.14-0.48), Germany (OR 2.75, 95% CI 1.55-4.86) and Estonia (OR 6.79, 95% CI 3.84-12.0). The odds of AP use decreased with the presence of a dementia specific unit inthe LTCF (OR 0.60, 95% CI 0.39-0.92), but was higher among residents with a hyperactivity behavior (OR 2.12, 95% CI 1.41-3.18).Conclusion: The current study shows that more than one-third of the residents recently admitted received APs and that prescription frequency across countries varied significantly. This study raises the possibility that the presence of a dementia-specific unit might play a role in the AP use. Further studies should investigate this association and seek better understanding of what will achieve optimal quality of AP use among newly admitted residents in LTCF. © 2014 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 7. |
- Hampton, Stephanie E., et al.
(författare)
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Ecology under lake ice
- 2017
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:1, s. 98-111
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Forskningsöversikt (refereegranskat)abstract
- Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.
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| 8. |
- Rahm Hallberg, Ingalill, et al.
(författare)
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Professional care providers in dementia care in eight European countries; their training and involvement in early dementia stage and in home care
- 2016
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Ingår i: Dementia. - London : Sage Publications. - 1471-3012 .- 1741-2684. ; 15:5, s. 931-957
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge concerning professionals involved in dementia care throughout its trajectory is sparse; the focus has mainly been on nursing-homecare and less on home care, diagnosis and treatment of the disease and its complications despite the fact that home care is the most prominent type of care. The aim of this study was to explore and describe professional care providers involved in dementia care and their educational level applying the International Standard Classification of Education (ISCED) and further to investigate practice in the RightTimePlaceCare-countrieswith regard to screening, diagnostic procedures and treatment of dementia and home care. The findings demonstrate more similarities than differences in terms of type of professionals involved among the countries although untrained staff were more common in some countries. Findings also show that many types of professionals are involved, who to turn to may not be clear, for instance in terms of medical specialities and it may be unclear who bears the ultimate responsibility. The professionals involved in diagnosis, treatment and care are educated to bachelor's level or above whilst everyday care is provided by people trained at a lower ISCED level or with no formal training. Registered nurses as well as occupational therapists have bachelor's degrees in most countries, but not in Germany or Estonia. Professionals specifically trained in dementia care are not so common. Further research is needed to reveal not only who provides the diagnostics and treatment, but also how home care is organised and quality assured. Many different types of professionals serve as providers along the trajectory of the disease which may be difficult for the patient and the informal caregiver to cope with. © The Author(s) 2014
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| 9. |
- Renom-Guiteras, Anna, et al.
(författare)
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Potentially inappropriate medication among people with dementia in eight European countries
- 2018
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 47:1, s. 68-74
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: to evaluate the frequency of potentially inappropriate medication (PIM) prescription among older people with dementia (PwD) from eight countries participating in the European study 'RightTimePlaceCare', and to evaluate factors and adverse outcomes associated with PIM prescription.Methods: survey of 2,004 PwD including a baseline assessment and follow-up after 3 months. Interviewers gathered data on age, sex, prescription of medication, cognitive status, functional status, comorbidity, setting and admission to hospital, fall-related injuries and mortality in the time between baseline and follow-up. The European Union(7)-PIM list was used to evaluate PIM prescription. Multivariate regression analysis was used to investigate factors and adverse outcomes associated with PIM prescription.Results: overall, 60% of the participants had at least one PIM prescription and 26.4% at least two. The PIM therapeutic subgroups most frequently prescribed were psycholeptics (26% of all PIM prescriptions) and 'drugs for acid-related disorders' (21%). PwD who were 80 years and older, lived in institutional long-term care settings, had higher comorbidity and were more functionally impaired were at higher risk of being prescribed two PIM or more. The prescription of two or more PIM was associated with higher chance of suffering from at least one fall-related injury and at least one episode of hospitalisation in the time between baseline and follow-up.Conclusions: PIM use among PwD is frequent and is associated with institutional long-term care, age, advanced morbidity and functional impairment. It also appears to be associated with adverse outcomes. Special attention should be paid to psycholeptics and drugs for acid-related disorders.
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| 10. |
- Risco, Ester, et al.
(författare)
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The association between physical dependency and the presence of neuropsychiatric symptoms, with the admission of people with dementia to a long-term care institution : A prospective observational cohort study
- 2015
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Ingår i: International Journal of Nursing Studies. - London : Elsevier. - 0020-7489 .- 1873-491X. ; 52:5, s. 980-987
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dementia is a progressive neurological disorder that causes a high degree of dependency. This dependency has been defined as an increased need for assistance due to deterioration in cognition and physicalfunctioning, and changes in behavior. Highly dependent people with dementia are more likely to be institutionalized.Objectives: To investigate the association between specific categories of physical dependency and the presence ofneuropsychiatric symptoms in people with dementia admitted to a long-term care institution.Design: A prospective observational cohort study.Settings: Home care and long-term care institutions in eight European countries.Participants: People with dementia living at home but at risk of institutionalization and recently institutionalized people with dementia.Method: Baseline and 3-month follow-up interviews were performed between November, 2010 and April, 2012. Thesample consisted of 116 recently institutionalized dementia sufferers and 949 people with dementia still living at home. Physical dependency was measured using the Katz Activity of Daily Living index, and neuropsychiatric symptoms were assessed through The Neuropsychiatric Inventory. Specific categories of dependency were analyzed by performing a logistic regression analysis. This followed examination of baseline characteristics to define the degree of physicaldependency, as factors associated with institutionalization, and evaluation of the same characteristics at 3-month follow-up to detect changes in the degree of physical dependency and neuropsychiatric symptoms associated with recent admission to a long-term care institution.Results: Toileting, dressing and continence dependency was higher in institutionalized people than in those receiving home-care. Delusion, hallucination, agitation, anxiety, apathy, motor-disturbances, night-time behavior and eating disorders were also worse in the institutionalized. Logistic regression analysis showed that independent factors significantly associated with being recently institutionalized were toileting (odds ratio = 2.3; 95% confidence interval = 1.43-3.71) and motor disturbances (odds ratio = 1.81; 95% confidence interval = 1.15-2.87).Conclusions: This study supports the association between type and degree of physical dependency in people with dementia and long-term institutionalization. Institutionalization is associated with physical dependency and the presenceof neuropsychiatric symptoms. (C) 2015 Elsevier Ltd. All rights reserved.
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