| 1. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
|
|
| 2. |
- Williamson, Alice, et al.
(författare)
-
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
-
Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
|
|
| 3. |
- Broadaway, K Alaine, et al.
(författare)
-
Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
-
Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
|
|
| 4. |
- Boström, Magnus, 1972-, et al.
(författare)
-
Conditions for Transformative Learning for Sustainable Development : A Theoretical Review and Approach
- 2018
-
Ingår i: Sustainability. - : MDPI. - 2071-1050. ; 10:12
-
Tidskriftsartikel (refereegranskat)abstract
- Continued unsustainability and surpassed planetary boundaries require not only scientific and technological advances, but deep and enduring social and cultural changes. The purpose of this article is to contribute a theoretical approach to understand conditions and constraints for societal change towards sustainable development. In order to break with unsustainable norms, habits, practices, and structures, there is a need for learning for transformation, not only adaption. Based on a critical literature review within the field of learning for sustainable development, our approach is a development of the concept of transformative learning, by integrating three additional dimensions—Institutional Structures, Social Practices, and Conflict Perspectives. This approach acknowledges conflicts on macro, meso, and micro levels, as well as structural and cultural constraints. It contends that transformative learning is processual, interactional, long-term, and cumbersome. It takes place within existing institutions and social practices, while also transcending them. The article adopts an interdisciplinary social science perspective that acknowledges the importance of transformative learning in order for communities, organizations, and individuals to be able to deal with global sustainability problems, acknowledging the societal and personal conflicts involved in such transformation.
|
|
| 5. |
- Gustafsson, Johan E., 1979-
(författare)
-
A Note in Defence of Ratificationism
- 2011
-
Ingår i: Erkenntnis. - : Springer Science and Business Media LLC. - 0165-0106 .- 1572-8420. ; 75:1, s. 147-150
-
Tidskriftsartikel (refereegranskat)abstract
- Andy Egan argues that neither evidential nor causal decision theorygives the intuitively right recommendation in the cases The Smoking Lesion, ThePsychopath Button, and The Three-Option Smoking Lesion. Furthermore, Eganargues that we cannot avoid these problems by any kind of ratificationism. Thispaper develops a new version of ratificationism that gives the right recommendations.Thus, the new proposal has an advantage over evidential and casual decisiontheory and standard ratificationist evidential decision theory.
|
|
| 6. |
- Gustafsson, Johan E., 1979
(författare)
-
A Paradox for the Intrinsic Value of Freedom of Choice
- 2020
-
Ingår i: Nous. - : Wiley. - 0029-4624. ; 54:4, s. 891-913
-
Tidskriftsartikel (refereegranskat)abstract
- A standard liberal claim is that freedom of choice is not only instrumentally valuable but also intrinsically valuable, that is, valuable for its own sake. I argue that each one of five conditions should hold if freedom of choice is intrinsically valuable: First, if rational people may differ as to which option is the most preferred in an option set, the offered freedom of choice has some intrinsic value. Second, if an option set is expanded with an option that must be less preferred than the already available options by any rational person, the intrinsic value of the offered freedom of choice does not increase. Third, if an option set is expanded, the intrinsic value of the offered freedom of choice does not decrease. Fourth, if an option set has only one option, it does not offer any intrinsically good freedom of choice. And, fifth, the relation ‘at least as good freedom of choice as’ is transitive. The trouble is that there exists a counter-example to the conjunction of these conditions. Hence freedom of choice is not intrinsicallyvaluable. © 2019 Wiley Periodicals, Inc.
|
|
| 7. |
- Gustafsson, Johan E., 1979, et al.
(författare)
-
A Simpler, More Compelling Money Pump with Foresight
- 2020
-
Ingår i: The Journal of Philosophy. - : Philosophy Documentation Center. - 0022-362X .- 1939-8549. ; 117:10, s. 578-589
-
Tidskriftsartikel (refereegranskat)abstract
- One might think that money pumps directed at agents with cyclic preferences can be avoided by foresight. This view was challenged two decades ago by the discovery of a money pump with foresight, which works against agents who use backward induction. But backward induction implausibly assumes that the agent would act rationally and retain her trust in her future rationality even at choice nodes that could only be reached if she were to act irrationally. This worry, however, does not apply to BI-terminating decision problems, where at each choice node backward induction prescribes a move that terminates further action. For BI-terminating decision problems, it is enough to assume that rationality and trust in rationality are retained at choice nodes reachable by rational moves. The old money pump with foresight was not BI-terminating. In this paper, we present a new money pump with foresight-one that is both BI-terminating and considerably simpler.
|
|
| 8. |
- Gustafsson, Johan E., 1979-
(författare)
-
An extended framework for preference relations
- 2011
-
Ingår i: Economics and Philosophy. - : Cambridge University Press (CUP). - 0266-2671 .- 1474-0028. ; 27:2, s. 101-108
-
Tidskriftsartikel (refereegranskat)abstract
- In order to account for non-traditional preference relations the present paper develops a new, richer framework for preference relations. This new framework provides characterizations of non-traditional preference relations, such as incommensurateness and instability, that may hold when neither preference nor indifference do. The new framework models relations with swaps, which are conceived of as transfers from one alternative state to another. The traditional framework analyses dyadic preference relations in terms of a hypothetical choice between the two compared alternatives. The swap framework extends this approach by analysing dyadic preference relations in terms of two hypothetical choices: the choice between keeping the first of the compared alternatives or swapping it for the second; and the choice between keeping the second alternative or swapping it for the first.
|
|
| 9. |
- Gustafsson, Johan E., 1979-
(författare)
-
An extended framework for preference relations–corrected version
- 2011
-
Ingår i: Economics and Philosophy. - 0266-2671 .- 1474-0028. ; 27:3, s. 360-367
-
Tidskriftsartikel (refereegranskat)abstract
- It is regretted that the originally published paper (doi:10.1017/S0266267111000010, published online 22 June 2011) was not the author's final amended version. We apologise for this oversight and reproduce the entire corrected paper here in print and online, with revised notation. In order to account for non-traditional preference relations the present paper develops a new, richer framework for preference relations. This new framework provides characterizations of non-traditional preference relations, such as incommensurateness and instability, that may hold when neither preference nor indifference do. The new framework models relations with swaps, which are conceived of as transfers from one alternative state to another. The traditional framework analyses dyadic preference relations in terms of a hypothetical choice between the two compared alternatives. The swap framework extends this approach by analysing dyadic preference relations in terms of two hypothetical choices: the choice between keeping the first of the compared alternatives or swapping it for the second; and the choice between keeping the second alternative or swapping it for the first.
|
|
| 10. |
- Gustafsson, Johan E., 1979
(författare)
-
Bentham's Mugging
- 2022
-
Ingår i: Utilitas. - 0953-8208. ; 34:4, s. 386-391
-
Tidskriftsartikel (refereegranskat)abstract
- A dialogue, in three parts, on utilitarian vulnerability to exploitation.
|
|
