| 1. |
|
|
| 2. |
- Glasbey, JC, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Postmus, I., et al.
(author)
-
Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
-
In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
-
Journal article (peer-reviewed)abstract
- Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
|
|
| 6. |
- Callaway, EM, et al.
(author)
-
A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
-
Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
|
|
| 7. |
- Postmus, Iris, et al.
(author)
-
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
- 2014
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5
-
Journal article (peer-reviewed)abstract
- Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.
|
|
| 8. |
|
|
| 9. |
- Kraja, Aldi T., et al.
(author)
-
New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
-
In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
-
Journal article (peer-reviewed)abstract
- Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
|
|
| 10. |
- Pattaro, Cristian, et al.
(author)
-
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
|
|
| 11. |
- Lagou, Vasiliki, et al.
(author)
-
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
|
|
| 12. |
- Peloso, Gina M, et al.
(author)
-
Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.
- 2014
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
-
Journal article (peer-reviewed)abstract
- Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.
|
|
| 13. |
- Moallemi, E. A., et al.
(author)
-
Evaluating Participatory Modeling Methods for Co-creating Pathways to Sustainability
- 2021
-
In: Earth's Future. - 2328-4277. ; 9:3
-
Journal article (peer-reviewed)abstract
- The achievement of global sustainability agendas, such as the Sustainable Development Goals, relies on transformational change across society, economy, and environment that are co-created in a transdisciplinary exercise by all stakeholders. Within this context, environmental and societal change is increasingly understood and represented via participatory modeling for genuine engagement with multiple collaborators in the modeling process. Despite the diversity of participatory modeling methods to promote engagement and co-creation, it remains uncertain what the extent and modes of participation are in different contexts, and how to select the suitable methods to use in a given situation. Based on a review of available methods and specification of potential contextual requirements, we propose a unifying framework to guide how collaborators of different backgrounds can work together and evaluate the suitability of participatory modeling methods for co-creating sustainability pathways. The evaluation of method suitability promises the integration of concepts and approaches necessary to address the complexities of problems at hand while ensuring robust methodologies based on well-tested evidence and negotiated among participants. Using two illustrative case studies, we demonstrate how to explore and evaluate the choice of methods for participatory modeling in varying contexts. The insights gained can inform creative participatory approaches to pathway development through tailored combinations of methods that best serve the specific sustainability context of particular case studies.
|
|
| 14. |
- Moallemi, E. A., et al.
(author)
-
Evaluating Participatory Modeling Methods for Co‐creating Pathways to Sustainability
- 2021
-
In: Earth's Future. - : American Geophysical Union (AGU). - 2328-4277. ; 9:3
-
Journal article (peer-reviewed)abstract
- The achievement of global sustainability agendas, such as the Sustainable Development Goals, relies on transformational change across society, economy, and environment that are co-created in a transdisciplinary exercise by all stakeholders. Within this context, environmental and societal change is increasingly understood and represented via participatory modeling for genuine engagement with multiple collaborators in the modeling process. Despite the diversity of participatory modeling methods to promote engagement and co-creation, it remains uncertain what the extent and modes of participation are in different contexts, and how to select the suitable methods to use in a given situation. Based on a review of available methods and specification of potential contextual requirements, we propose a unifying framework to guide how collaborators of different backgrounds can work together and evaluate the suitability of participatory modeling methods for co-creating sustainability pathways. The evaluation of method suitability promises the integration of concepts and approaches necessary to address the complexities of problems at hand while ensuring robust methodologies based on well-tested evidence and negotiated among participants. Using two illustrative case studies, we demonstrate how to explore and evaluate the choice of methods for participatory modeling in varying contexts. The insights gained can inform creative participatory approaches to pathway development through tailored combinations of methods that best serve the specific sustainability context of particular case studies.
|
|
| 15. |
- Raghavan, Maanasa, et al.
(author)
-
Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
-
Journal article (peer-reviewed)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
|
|
| 16. |
- Norström, Albert, et al.
(author)
-
Principles for knowledge co-production in sustainability research
- 2020
-
In: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 3:3, s. 182-190
-
Journal article (peer-reviewed)abstract
- Research practice, funding agencies and global science organizations suggest that research aimed at addressing sustainability challenges is most effective when 'co-produced' by academics and non-academics. Co-production promises to address the complex nature of contemporary sustainability challenges better than more traditional scientific approaches. But definitions of knowledge co-production are diverse and often contradictory. We propose a set of four general principles that underlie high-quality knowledge co-production for sustainability research. Using these principles, we offer practical guidance on how to engage in meaningful co-productive practices, and how to evaluate their quality and success. Research addressing sustainability issues is more effective if 'co-produced' by academics and non-academics, but definitions of co-production vary. This Perspective presents four knowledge co-production principles for sustainability research and guides on how to engage in co-productive practices.
|
|
| 17. |
- Chapin, III F.S., et al.
(author)
-
Resilience-based stewardship : Strategies for navigating sustainable pathways in a changing world.
- 2009
-
In: Principles of ecosystem stewardship. - New York : Springer Verlag. - 9780387730332 ; , s. 319-337
-
Book chapter (pop. science, debate, etc.)abstract
- Accelerated global changes in climate, environment, and social–ecological systems demand a transformation in human perceptions of our place in nature and patterns of resource use. The biology and culture of Homo sapiens evolved for about 95% of our species’ history in hunting-and-gathering societies before the emergence of settled agriculture. We have lived in complex societies for about 3%, and in industrial societies using fossil fuels for about 0.1% of our history. The pace of cultural evolution, including governance arrangements and resource-use patterns, appears insufficient to adjust to the rate and magnitude of technological innovations, human population increases, and environmental impacts that have occurred. Many of these changes are accelerating, causing unsustainable exploitation of ecosystems, including many boreal and tropical forests, drylands, and marine fisheries. The net effect has been serious degradation of the planet’s life-support system on which societal development ultimately depends (see Chapters 2 and 14.
|
|
| 18. |
- Seitzinger, Sybil P., et al.
(author)
-
Planetary Stewardship in an Urbanizing World : Beyond City Limits
- 2012
-
In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 41:8, s. 787-794
-
Journal article (peer-reviewed)abstract
- Cities are rapidly increasing in importance as a major factor shaping the Earth system, and therefore, must take corresponding responsibility. With currently over half the world's population, cities are supported by resources originating from primarily rural regions often located around the world far distant from the urban loci of use. The sustainability of a city can no longer be considered in isolation from the sustainability of human and natural resources it uses from proximal or distant regions, or the combined resource use and impacts of cities globally. The world's multiple and complex environmental and social challenges require interconnected solutions and coordinated governance approaches to planetary stewardship. We suggest that a key component of planetary stewardship is a global system of cities that develop sustainable processes and policies in concert with its non-urban areas. The potential for cities to cooperate as a system and with rural connectivity could increase their capacity to effect change and foster stewardship at the planetary scale and also increase their resource security.
|
|
