| 1. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 2. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 3. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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| 4. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 5. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 6. |
- Benedetto, Chiara, et al.
(författare)
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FIGO Preconception Checklist: Preconception care for mother and baby.
- 2024
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - 1879-3479.
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Tidskriftsartikel (refereegranskat)abstract
- The preconception period is a unique and opportunistic time in a woman's life when she is motivated to adopt healthy behaviors that will benefit her and her child, making this time period a critical "window of opportunity" to improve short- and long-term health. Improving preconception health can ultimately improve both fetal and maternal outcomes. Promoting health before conception has several beneficial effects, including an increase in seeking antenatal care and a reduction in neonatal mortality. Preconception health is a broad concept that encompasses the management of chronic diseases, including optimal nutrition, adequate consumption of folic acid, control of body weight, adoption of healthy lifestyles, and receipt of appropriate vaccinations. Use of the FIGO Preconception Checklist, which includes the key elements of optimal preconception care, will empower women and their healthcare providers to better prepare women and their families for pregnancy.
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| 7. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 8. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 9. |
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| 10. |
- Giménez-García, Angel, et al.
(författare)
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Pollination supply models from a local to global scale
- 2023
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Ingår i: Web Ecology. - 1399-1183. ; 23:2, s. 99-129
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Tidskriftsartikel (refereegranskat)abstract
- Ecological intensification has been embraced with great interest by the academic sector but is still rarely taken up by farmers because monitoring the state of different ecological functions is not straightforward. Modelling tools can represent a more accessible alternative of measuring ecological functions, which could help promote their use amongst farmers and other decision-makers. In the case of crop pollination, modelling has traditionally followed either a mechanistic or a data-driven approach. Mechanistic models simulate the habitat preferences and foraging behaviour of pollinators, while data-driven models associate georeferenced variables with real observations. Here, we test these two approaches to predict pollination supply and validate these predictions using data from a newly released global dataset on pollinator visitation rates to different crops. We use one of the most extensively used models for the mechanistic approach, while for the data-driven approach, we select from among a comprehensive set of state-of-The-Art machine-learning models. Moreover, we explore a mixed approach, where data-derived inputs, rather than expert assessment, inform the mechanistic model. We find that, at a global scale, machine-learning models work best, offering a rank correlation coefficient between predictions and observations of pollinator visitation rates of 0.56. In turn, the mechanistic model works moderately well at a global scale for wild bees other than bumblebees. Biomes characterized by temperate or Mediterranean forests show a better agreement between mechanistic model predictions and observations, probably due to more comprehensive ecological knowledge and therefore better parameterization of input variables for these biomes. This study highlights the challenges of transferring input variables across multiple biomes, as expected given the different composition of species in different biomes. Our results provide clear guidance on which pollination supply models perform best at different spatial scales-the first step towards bridging the stakeholder-Academia gap in modelling ecosystem service delivery under ecological intensification.
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| 11. |
- 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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| 12. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 13. |
- Killeen, Sarah Louise, et al.
(författare)
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Using FIGO Nutrition Checklist counselling in pregnancy: A review to support healthcare professionals.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479 .- 0020-7292. ; 160:Suppl 1, s. 10-21
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Forskningsöversikt (refereegranskat)abstract
- The period before and during pregnancy is increasingly recognized as an important stage for addressing malnutrition. This can help to reduce the risk of noncommunicable diseases in mothers and passage of risk to their infants. The FIGO Nutrition Checklist is a tool designed to address these issues. The checklist contains questions on specific dietary requirements, body mass index, diet quality, and micronutrients. Through answering these questions, awareness is generated, potential risks are identified, and information is collected that can inform health-promoting conversations between women and their healthcare professionals. The tool can be used across a range of health settings, regions, and life stages. The aim of this review is to summarize nutritional recommendations related to the FIGO Nutrition Checklist to support healthcare providers using it in practice. Included is a selection of global dietary recommendations for each of the components of the checklist and practical insights from countries that have used it. Implementation of the FIGO Nutrition Checklist will help identify potential nutritional deficiencies in women so that they can be addressed by healthcare providers. This has potential longstanding benefits for mothers and their children, across generations.
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| 14. |
- Loisel, Julie, et al.
(författare)
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A database and synthesis of northern peatland soil properties and Holocene carbon and nitrogen accumulation
- 2014
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Ingår i: The Holocene. - : SAGE Publications. - 0959-6836 .- 1477-0911. ; 24:9, s. 1028-1042
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Tidskriftsartikel (refereegranskat)abstract
- Here, we present results from the most comprehensive compilation of Holocene peat soil properties with associated carbon and nitrogen accumulation rates for northern peatlands. Our database consists of 268 peat cores from 215 sites located north of 45 degrees N. It encompasses regions within which peat carbon data have only recently become available, such as the West Siberia Lowlands, the Hudson Bay Lowlands, Kamchatka in Far East Russia, and the Tibetan Plateau. For all northern peatlands, carbon content in organic matter was estimated at 42 +/- 3% (standard deviation) for Sphagnum peat, 51 +/- 2% for non-Sphagnum peat, and at 49 +/- 2% overall. Dry bulk density averaged 0.12 +/- 0.07 g/cm(3), organic matter bulk density averaged 0.11 +/- 0.05 g/cm(3), and total carbon content in peat averaged 47 +/- 6%. In general, large differences were found between Sphagnum and non-Sphagnum peat types in terms of peat properties. Time-weighted peat carbon accumulation rates averaged 23 +/- 2 (standard error of mean) g C/m(2)/yr during the Holocene on the basis of 151 peat cores from 127 sites, with the highest rates of carbon accumulation (25-28 g C/m(2)/yr) recorded during the early Holocene when the climate was warmer than the present. Furthermore, we estimate the northern peatland carbon and nitrogen pools at 436 and 10 gigatons, respectively. The database is publicly available at https://peatlands.lehigh.edu.
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| 15. |
- MacKenzie, Alison, et al.
(författare)
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Dissolving the Dichotomies Between Online and Campus-Based Teaching : a Collective Response to The Manifesto for Teaching Online (Bayne et al. 2020)
- 2022
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Ingår i: Postdigital Science and Education. - : Springer. - 2524-4868 .- 2524-485X. ; , s. 271-329
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Tidskriftsartikel (refereegranskat)abstract
- This article is a collective response to the 2020 iteration of The Manifesto for Teaching Online. Originally published in 2011 as 20 simple but provocative statements, the aim was, and continues to be, to critically challenge the normalization of education as techno-corporate enterprise and the failure to properly account for digital methods in teaching in Higher Education. The 2020 Manifesto continues in the same critically provocative fashion, and, as the response collected here demonstrates, its publication could not be timelier. Though the Manifesto was written before the Covid-19 pandemic, many of the responses gathered here inevitably reflect on the experiences of moving to digital, distant, online teaching under unprecedented conditions. As these contributions reveal, the challenges were many and varied, ranging from the positive, breakthrough opportunities that digital learning offered to many students, including the disabled, to the problematic, such as poor digital networks and access, and simple digital poverty. Regardless of the nature of each response, taken together, what they show is that The Manifesto for Teaching Online offers welcome insights into and practical advice on how to teach online, and creatively confront the supremacy of face-to-face teaching.
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| 16. |
- MacKenzie, Alison, et al.
(författare)
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Dissolving the Dichotomies Between Online and Campus-Based Teaching : a Collective Response to The Manifesto for Teaching Online (Bayne et al. 2020)
- 2022
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Ingår i: Postdigital Science and Education. - : Springer. - 2524-4868 .- 2524-485X. ; 4, s. 271-329
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Tidskriftsartikel (refereegranskat)abstract
- This article is a collective response to the 2020 iteration of The Manifesto for Teaching Online. Originally published in 2011 as 20 simple but provocative statements, the aim was, and continues to be, to critically challenge the normalization of education as techno-corporate enterprise and the failure to properly account for digital methods in teaching in Higher Education. The 2020 Manifesto continues in the same critically provocative fashion, and, as the response collected here demonstrates, its publication could not be timelier. Though the Manifesto was written before the Covid-19 pandemic, many of the responses gathered here inevitably reflect on the experiences of moving to digital, distant, online teaching under unprecedented conditions. As these contributions reveal, the challenges were many and varied, ranging from the positive, breakthrough opportunities that digital learning offered to many students, including the disabled, to the problematic, such as poor digital networks and access, and simple digital poverty. Regardless of the nature of each response, taken together, what they show is that The Manifesto for Teaching Online offers welcome insights into and practical advice on how to teach online, and creatively confront the supremacy of face-to-face teaching.
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| 17. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 18. |
- Minelli, Caterina, et al.
(författare)
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Versailles project on advanced materials and standards (VAMAS) interlaboratory study on measuring the number concentration of colloidal gold nanoparticles
- 2022
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Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 14, s. 4690-4704
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Tidskriftsartikel (refereegranskat)abstract
- We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol. We find that the population-averaging methods of SAXS, CLS and UV-Vis have high measurement repeatability and reproducibility, with between-labs variability of 2.6%, 11% and 1.4% respectively. However, results may be significantly biased for reasons including inaccurate material properties whose values are used to compute the number concentration. Particle-counting method results are less reproducibile than population-averaging methods, with measured between-labs variability of 68% and 46% for PTA and spICP-MS respectively. This study provides the stakeholder community with important comparative data to underpin measurement reproducibility and method validation for number concentration of nanoparticles.
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| 19. |
- O'Reilly, Éilis J, et al.
(författare)
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Prediagnostic body size and risk of amyotrophic lateral sclerosis death in 10 studies
- 2018
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa UK Limited. - 2167-8421 .- 2167-9223. ; 19:5-6, s. 396-406
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES AND METHODS: Using pooled multivariable-adjusted rate ratios (RR), we explored relationships between prediagnostic body-mass-index (BMI), waist-to-hip-ratio (WHR), and weight-gain during adulthood, and ALS in 419,894 women and 148,166 men from 10 community-based cohorts in USA, Europe, and Australia; 428 ALS deaths were documented in women and 204 in men.RESULTS: , limiting power. Weight-gain during adulthood was strongly associated with lower ALS; for an additional 1kg gain in weight/year, the RR = 0.43 (95% CI: 0.28-0.65; p < 0.001). Associations persisted when adjusted for diabetes at enrollment, restricted to never-smokers, and ALS deaths in the 5 years after enrollment were excluded (accounting for recent weight loss).CONCLUSIONS: These findings confirm somewhat conflicting, underpowered evidence that adiposity is inversely associated with ALS. We newly demonstrate that weight-gain during adulthood is strongly predictive of lower ALS risk.
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| 20. |
- Wang, Thomas J, et al.
(författare)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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Ingår i: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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