| 1. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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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. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 4. |
- 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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| 5. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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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.
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| 6. |
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| 7. |
- Goossen, Mikael, 1988-
(författare)
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In his or her opinion? : the gender gap in attitudes toward the welfare state in Sweden and Europe
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background This thesis explores differences in the attitudes that men and women hold toward the welfare state by investigating previously neglected areas concerning how attitudes differ between welfare states, as well as the role played by emotional and psychological attachment to a gender group. The studies analyze how gender differences in welfare state attitudes relate to social policies and prevailing gender relations, as well as to the process of social identification with a gender group. They also provide evidence on the longitudinal development of attitudinal gender differences in Sweden.Methods All four studies rely on survey data. One part of this thesis consists of a comparison between countries in Europe that utilizes a multilevel analysis to examine how the interaction between family policy and gender (in)equalities in the division of unpaid labor is related to gender differences in support for the government’s responsibility to provide social welfare. A second part consists of analyzing trends in multiple attitudes toward the Swedish welfare state, covering both normative and evaluative aspects of welfare state support for the years 1981–2018. A third part consists of examining welfare state attitudes in Sweden during the year 2018. Here, the focus is on social identification with a gender group and its potential role as an intermediary factor in the relationship between gender and welfare state attitudes. Results The gender gap in people’s support for the government’s role in providing social welfare varies among European countries, with attitudes differing most in countries where men and women share more equally in performing unpaid care and domestic labor. Conversely, men and women do not display differences in their welfare state attitudes in countries where inequalities in the division of unpaid labor are widespread. However, the relationship between gender (in)equality in unpaid labor and welfare state attitudes is shaped by the institutional design. In countries where family policies subsidize women’s caregiving within families without public alternatives—thus normatively conveying the resulting gender inequalities as corresponding to inherent differences in caregiving capabilities—this relationship does not exist. The last four decades of attitudes toward the Swedish welfare state demonstrate no clear trends revealing whether gender differences are diverging or converging; nevertheless, the correlational evidence of contextual variation in the attitudinal gender gap speaks in favor of progression in gender equality as being coupled with larger attitudinal differences. Regarding social identification with a gender group, this process is not connected with observed gender differences in people’s suspicion of welfare overuse in Sweden. However, when compared with both women and other men, men with a strong gender identification are less willing to increase social spending in Sweden. The observed relationships match the predictions made when theorizing social identification with a gender group as enhancing attentiveness to gendered self-interest among men under conditions of potential masculinity threat and thus increasing the likelihood of adopting stereotypically masculine attitudes toward equality and social welfare. Conclusions Gender differences in welfare state attitudes are not universal. An integrated theory of gender differences in welfare state attitudes should account for the interplay between structuring aspects of the welfare state and prevailing gender norms, and how these relate to psychological aspects of gender as a social identity. Attitudinal gender differences should therefore be understood in terms of what type of welfare state men and women are expressing their attitudes toward and how this welfare state affects gender relations. Attachment to their gender group seems to be of special importance for men’s attitudes. However, this is only true for dimensions where the welfare state can be viewed as a threat to masculinity by undercutting the normative connection between masculinity and breadwinning.
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| 8. |
- Hardell, Sanna, et al.
(författare)
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Welfare service privatization and opinions about service quality : The role of political ideology among local politicians and the public
- 2020
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Ingår i: Social Policy & Administration. - : Wiley-Blackwell Publishing Inc.. - 0144-5596 .- 1467-9515. ; 54:1, s. 45-59
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Tidskriftsartikel (refereegranskat)abstract
- In this article, we join the discussion about the potential consequences of welfare service privatization by examining the relationship between the privatization of welfare service delivery and public opinion about service quality in Sweden. Due to the politically polarized debate about welfare service privatization in Sweden, we also examine the extent to which individuals' ideological orientations influence this relationship in both local politicians and ordinary citizens. For local politicians, the results show that a higher municipal degree of privatization is generally associated with slightly lower levels of satisfaction overall with welfare services, although no such relationship exists for the public. Most importantly, however, the results indicate that political ideology constitutes an important moderator in the relationship between privatization and opinions about service quality. Local politicians and, to some extent, ordinary citizens who place themselves to the left on the ideological left–right scale tend to be less satisfied with services as the municipal degree of welfare service privatization increases. For local politicians who position themselves far to the right on the scale, the relationship between welfare service privatization and satisfaction is positive. These findings suggest that there is no clear-cut relationship between privatization and individuals' opinions about services; rather, this relationship depends on the ideological predispositions of local politicians and ordinary citizens.
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| 9. |
- Häggström, Ida, 1982-, et al.
(författare)
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A Monte Carlo study of the dependence of early frame sampling on uncertainty and bias in pharmacokinetic parameters from dynamic PET
- 2015
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Ingår i: Journal of Nuclear Medicine Technology. - : Society of Nuclear Medicine. - 0091-4916 .- 1535-5675. ; 43:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Compartmental modeling of dynamic PET data enables quantifi- cation of tracer kinetics in vivo, through the calculated model parameters. In this study, we aimed to investigate the effect of early frame sampling and reconstruction method on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias and uncertainty (SD). Methods: The GATE Monte Carlo software was used to simulate 2 · 15 dynamic 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) brain PET studies, typical in terms of noise level and kinetic parameters. The data were reconstructed by both 3- dimensional (3D) filtered backprojection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6 dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15 s. Bias and SD were evaluated for fitted parameter estimates, calculated from regions of interest. Results: The 2-tissue-model parameter estimates K1, k2, and fraction of arterial blood in tissue depended on early frame sampling, and a sampling of 6–15 s generally minimized bias and SD. The shortest sampling of 1 s yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM, respectively, and a parameter uncertainty that was 10%–70% higher. The schemes from 4 to 15 s were generally not significantly different in regards to bias and SD. Typically, the reconstruction method 3DRP yielded less framesampling dependence and less uncertain results, compared with OSEM, but was on average more biased. Conclusion: Of the 6 sampling schemes investigated in this study, an early frame duration of 6–15 s generally kept both bias and uncertainty to a minimum, for both 3DRP and OSEM reconstructions. Veryshort frames of 1 s should be avoided because they typically resulted in the largest parameter bias and uncertainty. Furthermore, 3DRP may be p
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| 10. |
- Häggström, Ida, 1982-
(författare)
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Quantitative methods for tumor imaging with dynamic PET
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- There is always a need and drive to improve modern cancer care. Dynamic positron emission tomography (PET) offers the advantage of in vivo functional imaging, combined with the ability to follow the physiological processes over time. In addition, by applying tracer kinetic modeling to the dynamic PET data, thus estimating pharmacokinetic parameters associated to e.g. glucose metabolism, cell proliferation etc., more information about the tissue's underlying biology and physiology can be determined. This supplementary information can potentially be a considerable aid when it comes to the segmentation, diagnosis, staging, treatment planning, early treatment response monitoring and follow-up of cancerous tumors.We have found it feasible to use kinetic parameters for semi-automatic tumor segmentation, and found parametric images to have higher contrast compared to static PET uptake images. There are however many possible sources of errors and uncertainties in kinetic parameters obtained through compartment modeling of dynamic PET data. The variation in the number of detected photons caused by the random nature of radioactive decay, is of course always a major source. Other sources may include: the choice of an appropriate model that is suitable for the radiotracer in question, camera detectors and electronics, image acquisition protocol, image reconstruction algorithm with corrections (attenuation, random and scattered coincidences, detector uniformity, decay) and so on. We have found the early frame sampling scheme in dynamic PET to affect the bias and uncertainty in calculated kinetic parameters, and that scatter corrections are necessary for most but not all parameter estimates. Furthermore, analytical image reconstruction algorithms seem more suited for compartment modeling applications compared to iterative algorithms.This thesis and included papers show potential applications and tools for quantitative pharmacokinetic parameters in oncology, and help understand errors and uncertainties associated with them. The aim is to contribute to the long-term goal of enabling the use of dynamic PET and pharmacokinetic parameters for improvements of today's cancer care.
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