1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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2. |
- Abidi, Latifa, et al.
(författare)
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Conversations about alcohol in healthcare : cross-sectional surveys in the Netherlands and Sweden
- 2020
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Ingår i: BMC Public Health. - : BioMed Central. - 1471-2458. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThis study evaluated and compared the extent, duration, contents, experiences and effects of alcohol conversations in healthcare in the Netherlands and Sweden in 2017.MethodsSurvey data in the Netherlands and Sweden were collected through an online web panel. Subjects were 2996 participants (response rate: 50.8%) in Sweden and 2173 (response rate: 82.2%) in the Netherlands. Data was collected on socio-demographics, alcohol consumption, healthcare visits in the past 12 months, number of alcohol conversations, and characteristics of alcohol conversations (duration, contents, experience, effects).ResultsResults showed that Swedish respondents were more likely to have had alcohol conversations (OR = 1.99; 95%CI = 1.64–2.41; p = < 0.001) compared to Dutch respondents. In Sweden, alcohol conversations were more often perceived as routine (p = < 0.001), were longer (p = < 0.001), and more often contained verbal information about alcohol’s health effects (p = 0.007) or written information (p = 0.001) than in the Netherlands. In Sweden, 40+ year-olds were less likely to report a positive effect compared to the youngest respondents. In the Netherlands, men, sick-listed respondents, and risky drinkers, and in Sweden those that reported “other” occupational status such as parental leave, were more likely to have had alcohol conversations.ConclusionsThe results suggest that alcohol conversations are more common in healthcare practice in Sweden than in the Netherlands. However, positive effects of alcohol conversations were less likely to be reported among older respondents in Sweden. Our results indicate that alcohol preventative work should be improved in both countries, with more focus on risky drinkers and the content of the conversations in Sweden, and expanding alcohol screening in the Netherlands.
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3. |
- Cheng, Susan, et al.
(författare)
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Distinct metabolomic signatures are associated with longevity in humans.
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in metabolism influence lifespan in experimental models, but data in humans are lacking. Here we use liquid chromatography/mass spectrometry to quantify 217 plasma metabolites and examine their relation to longevity in a large cohort of men and women followed for up to 20 years. We find that, higher concentrations of the citric acid cycle intermediate, isocitrate, and the bile acid, taurocholate, are associated with lower odds of longevity, defined as attaining 80 years of age. Higher concentrations of isocitrate, but not taurocholate, are also associated with worse cardiovascular health at baseline, as well as risk of future cardiovascular disease and death. None of the metabolites identified are associated with cancer risk. Our findings suggest that some, but not all, metabolic pathways related to human longevity are linked to the risk of common causes of death.
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4. |
- Cheng, Susan, et al.
(författare)
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Metabolite Profiling Identifies Pathways Associated With Metabolic Risk in Humans
- 2012
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Ingår i: Circulation. - 1524-4539. ; 125:18, s. 132-2222
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Tidskriftsartikel (refereegranskat)abstract
- Background-Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood. Methods and Results-To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmo Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, -0.04 to -0.22 per 1-SD change in log-glutamine; P<0.001), glutamate (0.05 to 0.14; P<0.001), and the glutamine-toglutamate ratio (-0.05 to -0.20; P<0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-to-glutamate ratio was associated with lower risk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted P=0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance (P=0.01) and decreased blood pressure (P=0.05). Conclusions-Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice. (Circulation. 2012;125:2222-2231.)
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5. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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6. |
- Karlsson, Nadine, et al.
(författare)
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Addressing alcohol in routine healthcare in Sweden-population-based surveys in 2010 and 2017
- 2019
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Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 29:4, s. 748-753
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aim of the study was to compare how alcohol was addressed in routine healthcare practice in Sweden in 2010 and 2017, following the 2011 implementation of national drinking guidelines.MethodsPopulation-based cross-sectional surveys were conducted in 2010 and in 2017. Subjects were 3200 respondents in 2010 (response rate 54%) and 3000 respondents in 2017 (response rate 51%) in Sweden. Both the 2010 and 2017 surveys collected data on: socio-demographics; alcohol consumption; healthcare visits in the past 12 months and characteristics of alcohol conversations in healthcare (duration, contents, experience and effects).ResultsIt was significantly more likely that respondents had a conversation about alcohol in healthcare in 2017 than in 2010 (OR = 1.49; 95% CI = 1.27–1.75; P<0.001). Conversations about alcohol in the healthcare were mostly short (<4 min), both in 2010 and 2017. The alcohol conversations in 2017 included less information about alcohol’s influence on health (P = 0.002) compared with 2010. The experience of the conversation about alcohol was perceived as less dramatic in 2017 than in 2010 (P = 0.038).ConclusionsThe results suggest that conversations about alcohol were more embedded in routine healthcare practice in Sweden in 2017 than in 2010. This development has occurred since the 2011 publication of the national guidelines. Alcohol conversations targeted also specific groups of drinkers as recommended by the guidelines. However, our study design does not allow for conclusions about the relationship between the guidelines and the changes in healthcare practice.
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7. |
- Karlsson, Nadine, et al.
(författare)
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Public perceptions of how alcohol consumption is dealt with in Swedish and Norwegian health care
- 2021
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Ingår i: Nordic Studies on Alcohol and Drugs. - : Sage Publications. - 1455-0725 .- 1458-6126. ; 38:3, s. 243-255
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aims of this study were to evaluate and compare popular beliefs and attitudes regarding alcohol conversations in healthcare in Sweden and Norway; and to explore which factors were associated with different levels of support for alcohol-prevention work in the two countries. Methods: Population-based cross-sectional surveys were conducted in Sweden (n = 3000) and Norway (n = 1208). Logistic regression was used to identify the characteristics of participants who were supportive of routine alcohol screening and brief intervention delivery. Results: A higher proportion of Swedish respondents agreed to a large extent that healthcare professionals should routinely ask about alcohol consumption. In addition, a higher proportion of Swedish respondents compared to respondents from Norway agreed that healthcare providers should only ask about patients alcohol consumption if this was related to specific symptoms. There were similar correlates of being supportive of routine alcohol screening and brief intervention delivery in both countries. Support was lower in both countries amongst moderate and risky drinkers, and among single adults or those on parental leave, but higher amongst older individuals. Having had an alcohol conversation in healthcare increased the level of support for alcohol prevention in routine healthcare among risky drinkers. Conclusions: There is a high level of support for preventative alcohol conversations in routine healthcare in Norway and Sweden, although there was a lower proportion of respondents who were positive to alcohol prevention in routine healthcare in Norway compared to Sweden. Experiencing alcohol conversation may positively affect risky drinkers attitudes towards and support for alcohol prevention. Thus, more frequent alcohol conversations in routine healthcare may also result in increased level of support for alcohol prevention among risky drinkers.
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8. |
- Karlsson, Nadine, 1965-, et al.
(författare)
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Relationship Between Educational Level and Attitudes Towards Alcohol Conversations in Healthcare : A Cross-Sectional Survey Conducted in Four European Countries
- 2023
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Ingår i: International Journal of Public Health. - : Frontiers Media S.A.. - 1661-8556 .- 1661-8564. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To examine the association between educational level and attitudes towards alcohol conversations in healthcare using population-based surveys of adults in England, the Netherlands, Norway, and Sweden; and to compare attitudes towards alcohol conversations in healthcare between these four countries. Methods: Cross-sectional surveys were conducted amongst adults in the general population in England (n = 3,499), the Netherlands (n = 2,173), Norway (n = 1,208), and Sweden (n = 3,000). Logistic regression analysis was used to examine associations between attitudes towards alcohol conversations in healthcare and educational level, key demographic variables, alcohol consumption, and country of residence. Results: In all four countries, low educational level (p < 0.001) and male gender (p < 0.001) were associated with holding negative attitudes towards discussing alcohol in healthcare. Risky drinkers had more negative attitudes than low risky drinkers towards discussing alcohol in healthcare (p < 0.001) in all countries except England (p = 0.48), and also reported low levels of perceived honesty and confidence in healthcare (p < 0.001). Conclusion: These findings highlight the importance of considering patients’ socio-economic status when developing and implementing alcohol prevention interventions in healthcare. Copyright © 2023 Karlsson, Skagerström, O’Donnell, Abidi, Thomas, Nilsen and Lid.
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9. |
- Kathiresan, Sekar, et al.
(författare)
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Common variants at 30 loci contribute to polygenic dyslipidemia
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 56-65
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Tidskriftsartikel (refereegranskat)abstract
- Blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels are risk factors for cardiovascular disease. To dissect the polygenic basis of these traits, we conducted genome-wide association screens in 19,840 individuals and replication in up to 20,623 individuals. We identified 30 distinct loci associated with lipoprotein concentrations (each with P < 5 x 10(-8)), including 11 loci that reached genome-wide significance for the first time. The 11 newly defined loci include common variants associated with LDL cholesterol near ABCG8, MAFB, HNF1A and TIMD4; with HDL cholesterol near ANGPTL4, FADS1-FADS2-FADS3, HNF4A, LCAT, PLTP and TTC39B; and with triglycerides near AMAC1L2, FADS1-FADS2-FADS3 and PLTP. The proportion of individuals exceeding clinical cut points for high LDL cholesterol, low HDL cholesterol and high triglycerides varied according to an allelic dosage score (P < 10(-15) for each trend). These results suggest that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia.
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