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- de Rojas, I., et al.
(författare)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- Davies, G., et al.
(författare)
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Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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- Komatsu, Kimberly J., et al.
(författare)
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Global change effects on plant communities are magnified by time and the number of global change factors imposed
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:36, s. 17867-17873
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Tidskriftsartikel (refereegranskat)abstract
- Accurate prediction of community responses to global change drivers (GCDs) is critical given the effects of biodiversity on ecosystem services. There is consensus that human activities are driving species extinctions at the global scale, but debate remains over whether GCDs are systematically altering local communities worldwide. Across 105 experiments that included over 400 experimental manipulations, we found evidence for a lagged response of herbaceous plant communities to GCDs caused by shifts in the identities and relative abundances of species, often without a corresponding difference in species richness. These results provide evidence that community responses are pervasive across a wide variety of GCDs on long-term temporal scales and that these responses increase in strength when multiple GCDs are simultaneously imposed.Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
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| 8. |
- Ottová-Jordan, Veronika, et al.
(författare)
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Trends in health complaints from 2002 to 2010 in 34 countries and their association with health behaviours and social context factors at individual and macro-level
- 2015
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 25:Suppl 2, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This article describes trends and stability over time in health complaints in adolescents from 2002 to 2010 and investigates associations between health complaints, behavioural and social contextual factors at individual level and economic factors at macro-level.METHODS: Comprising N = 510 876 11-, 13- and 15-year-old children and adolescents in Europe, North America and Israel, data came from three survey cycles of the international Health Behaviour in School-aged Children (HBSC) study. Age- and gender-adjusted trends in health complaints were examined in each country by means of linear regression. By using the country as the random effects variable, we tested to what extent individual and contextual variables were associated with health complaints.RESULTS: Significant associations are stronger for individual level determinants (e.g. being bullied, smoking) than for determinants at macro-level (e.g. GDP, Gini), as can be seen by the small effect sizes (less than 5% for different trends). Health complaints are fairly stable over time in most countries, and no clear international trend in health complaints can be observed between 2002 and 2010. The most prominent stable determinants were being female, being bullied, school pressure and smoking.CONCLUSION: Factors associated with health complaints are more related to the proximal environment than to distal macro-level factors. This points towards intensifying targeted interventions, (e.g. for bullying) and also targeting specific risk groups. The comparably small effect size at country-level indicates that country-level factors have an impact on health and should not be ignored.
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| 9. |
- Ottová-Jordan, Veronika, et al.
(författare)
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Trends in Multiple Recurrent health complaitns in 15-year-olds in 35 countries in Europe, North America and Israel from 1994 to 2010
- 2015
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 25:suppl 2, s. 24-27
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Health complaints are a good indicator of an individual's psychosocial health and well-being. Studies have shown that children and adolescents report health complaints which can cause significant individual burden. METHODS: Using data from the international Health Behaviour in School-aged Children study, this article describes trends in multiple recurrent health complaints (MHC) in 35 countries among N = 237 136 fifteen-year-olds from 1994 to 2010. MHC was defined as the presence of two or more health complaints at least once a week. Logistic regression analysis was performed to evaluate trends across the five survey cycles for each country. RESULTS: Lowest prevalence throughout the period 1994-2010 was 16.9% in 1998 in Austria and highest in 2006 in Israel (54.7%). Overall, six different trend patterns could be identified: No linear or quadratic trend (9 countries), linear decrease (7 countries), linear increase (5 countries), U-shape (4 countries), inverted U-shape (6 countries) and unstable (4 countries). CONCLUSION: Trend analyses are valuable in providing hints about developments in populations as well as for benchmarking and evaluation purposes. The high variation in health complaints between the countries requires further investigation, but may also reflect the subjective nature of health complaints.
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