| 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. |
- Van Bavel, Jay J., et al.
(författare)
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National identity predicts public health support during a global pandemic
- 2022
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Ingår i: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
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| 3. |
- Azevedo, Flavio, et al.
(författare)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
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Ingår i: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 4. |
- Breeur, Marie, et al.
(författare)
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Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition
- 2022
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Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations.Methods: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty.Results: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk.Conclusions: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
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| 5. |
- Castañeda, Jazmin, et al.
(författare)
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Association between classes and subclasses of polyphenol intake and 5-year body weight changes in the EPIC-PANACEA study
- 2023
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Ingår i: Obesity. - : John Wiley & Sons. - 1930-7381 .- 1930-739X. ; 31:4, s. 1146-1158
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to evaluate the associations among the intake of total polyphenols, polyphenol classes, and polyphenol subclasses and body weight change over 5 years.Methods: A total of 349,165 men and women aged 25 to 70 years were recruited in the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (PANACEA) project of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries. Body weight was measured at baseline and at follow-up after a median time of 5 years. Polyphenol intake, including four main polyphenol classes and eighteen subclasses, was estimated using validated dietary questionnaires and Phenol-Explorer. Multilevel mixed linear regression models were used to estimate the associations.Results: Participants gained, on average, 2.6 kg (±5.0 kg) over 5 years. Total flavonoids intake was inversely associated with body weight change (−0.195 kg/5 years, 95% CI: −0.262 to −0.128). However, the intake of total polyphenols (0.205 kg/5 years, 95% CI: 0.138 to 0.272) and intake of hydroxycinnamic acids (0.324 kg/5 years, 95% CI: 0.267 to 0.381) were positively associated with body weight gain. In analyses stratified by coffee consumption, hydroxycinnamic acid intake was positively associated with body weight gain in coffee consumers (0.379 kg/5 years, 95% CI: 0.319 to 0.440), but not in coffee nonconsumers (−0.179 kg/5 years, 95% CI: −0.490 to 0.133).Conclusions: Higher intakes of flavonoids and their subclasses are inversely associated with a modest body weight change. Results regarding hydroxycinnamic acids in coffee consumers require further investigation.
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| 6. |
- Dagnino, Sonia, et al.
(författare)
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Prospective identification of elevated circulating CDCP1 in patients years before onset of lung cancer
- 2021
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 81:13, s. 3738-3748
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer–related dysregulation of CDCP1 expression years before diagnosis.
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| 7. |
- Forouhi, Nita G., et al.
(författare)
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Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes : The EPIC-InterAct Case-Cohort Study
- 2016
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 13:7
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Tidskriftsartikel (refereegranskat)abstract
- Background Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.Methods and Findings Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, a-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with.-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs.Conclusions These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.
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| 8. |
- Geale, Kirk, 1988-
(författare)
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Associations between patient characteristics and outcomes in psoriatic disease : evidence from Swedish real-world data
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundPsoriatic disease, encompassing skin psoriasis and psoriatic arthritis, is a common condition affecting 2-3% of the Western population associated with reduced quality of life and increased healthcare costs. To improve patients’ lives and the stewardship of societal resources, a nuanced understanding of the associations between patient characteristics and health outcomes are needed for optimal clinical and societal decision making. While randomised clinical trials play a central role in evidence-based medicine, they have limitations relating to patient selection, follow-up duration, and idealised clinical conditions. In recent years, the role of real-world evidence in health research has grown, including in dermatology, due in part to its ability to describe and compare patients in routine clinical care. This thesis contains four analyses using Swedish real-world data describing associations between patient characteristics and outcomes in psoriatic disease.MethodsData from several administrative population registers in Sweden and the clinical registry PsoReg were collected for those with psoriatic disease in routine clinical care and linked at the patient level. The data include diagnoses, pharmacy dispensed medications, mortality, socioeconomic information, quality of life, and clinical severity. A matched non-psoriatic control group was also extracted.The first analysis assessed the association between disease severity (measured by the Psoriasis Area and Severity Index [PASI]) and health-related quality of life (measured the EuroQol 5-dimension instrument [EQ-5D]) in 2,674 patients with longitudinal follow-up in PsoReg, a fixed effects regression model was deployed adjusting for confounding factors including certain types of unobserved confounding. Second, the independent associations of skin psoriasis and somatic comorbidity with incident psychiatric illness were described across 93,239 psoriasis patients and 1.4 million controls. Their individual contributions and synergistic interaction were assessed using a time-to-event model. Diagnosis codes were used to construct the composite psychiatric illness outcome consisting of depression, anxiety, and suicidality. Diagnosis codes were also used to create the Elixhauser and Charlson comorbidity indexes to measure somatic comorbidity. The third analysis assessed age-related inequities in biologic prescriptions in 1,465 patients enrolled in PsoReg using a time-to-event analysis controlling for decision-making variables including disease severity. The analysis also described the non-parametric relationship between age and incident biologic prescriptions using a kernel regression.Finally, the fourth analysis describes rates of non-persistence in individuals with psoriatic arthritis treated with adalimumab, ustekinumab, and secukinumab using a time-to-event model. A total of 4,649 drug exposure period across 3,918 patients were assessed. Non-persistence was defined as a treatment switch or discontinuation, the latter defined as a failure to refill an existing prescription within two times the days of drug supplied.ResultsThe analysis found a statistically significant, negative association between PASI and the EQ-5D ( =-0.0186, 95% confidence interval [CI]: -0.0360, -0.0201) which was non-linear ( =0.0003, 95% confidence interval [CI]: 0.0001, 0.0004). Incremental PASI improvements for those with less skin involvement were associated with larger increases in quality of life than in those with more skin involvement. Skin psoriasis was found to be independently associated with the onset of psychiatric illness (hazard ratio [HR]=1.32, 95% CI: 1.27-1.36) as was somatic comorbidity (HR=2.09, 95%CI: 2.06-2.13). However, the results were compatible with a lack of synergistic effect between skin psoriasis and somatic comorbidity on psychiatric illness (HR=0.93; 95% CI: 0.81-1.04).Older psoriasis patients appeared less likely to initiate biologic therapies than their younger counterparts after controlling for disease severity and comorbidity (HR=0.97, 95% CI: 0.95-0.99).Individuals with psoriatic arthritis treated with ustekinumab were found to have lower rates of non-persistence compared to adalimumab (HR=0.56, 95% CI: 0.49-0.64). Secukinumab and adalimumab appeared to have similar rates of non-persistence (HR=1.01, 95% CI: 0.88-1.15), although the results differed in biologic-naïve and biologic-experienced subgroups. The definition of discontinuation was sensitive and had material effects on the results.ConclusionsPatient characteristics appear to play an important role in a variety of health outcomes in psoriatic disease, demonstrated across four real-world settings. The utilisation of data from routine clinical care enabled the investigation of research questions that are not suitable for clinical trial contexts, providing relevance for patients in everyday clinical practice. The study designs and methodologies applied in this thesis are associated with a variety of strengths and limitations, many of which are closely linked to the observational nature of the data, which have material importance for the interpretation of the results and implications for healthcare and policy. Understanding the associations between patient characteristics and subsequent outcomes is an important element in the delivery of holistic, personalised healthcare.
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| 9. |
- Gil-Lespinard, Mercedes, et al.
(författare)
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Dietary intake of 91 individual polyphenols and 5-year body weight change in the EPIC-PANACEA cohort
- 2022
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Ingår i: Antioxidants. - : MDPI. - 2076-3921. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Polyphenols are bioactive compounds from plants with antioxidant properties that may have a protective role against body weight gain, with adipose tissue and systemic oxidative stress as potential targets. We aimed to investigate the dietary intake of individual polyphenols and their association with 5-year body weight change in a sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 349,165 adult participants from nine European countries. Polyphenol intake was estimated through country-specific validated dietary questionnaires and the Phenol-Explorer database. Body weight was obtained at recruitment and after a mean follow-up time of 5 years. Associations were estimated using multilevel mixed linear regression models. From 91 polyphenols included, the majority (n = 67) were inversely associated with 5-year body weight change after FDR-correction (q < 0.05). The greatest inverse associations were observed for quercetin 3-O-rhamnoside (change in weight for doubling in intake: −0.071 (95% CI: −0.085; −0.056) kg/5 years). Only 13 polyphenols showed positive associations with body weight gain, mainly from the subclass hydroxycinnamic acids (HCAs) with coffee as the main dietary source, such as 4-caffeoylquinic acid (0.029 (95% CI: 0.021; 0.038) kg/5 years). Individual polyphenols with fruit, tea, cocoa and whole grain cereals as the main dietary sources may contribute to body weight maintenance in adults. Individual HCAs may have different roles in body weight change depending on their dietary source.
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| 10. |
- Girolomoni, Giampiero, et al.
(författare)
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Increasing Access to Effective Systemic Treatments in Patients with Moderate-to-Severe Psoriasis : Narrative Review
- 2023
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Ingår i: Dermatology and Therapy. - 2193-8210. ; 13:10, s. 2171-2185
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Forskningsöversikt (refereegranskat)abstract
- Psoriasis is a chronic, immune-mediated inflammatory disease with a worldwide prevalence ranging between 0.51 and 11.43%. It results in a large clinical and social burden, with patients frequently suffering from reduced quality of life, psychologic distress and debilitating comorbidities. Biologic agents are used to establish and maintain disease control in patients with moderate-to-severe psoriasis and are essential to improving quality of life. However, a substantial proportion of patients have limited access to therapy due to economics, health policies and clinical considerations, which creates clinical unmet needs that disadvantage both patients and healthcare professionals. Biosimilars are a cost-effective alternative to off-patent biologic therapies, and there is mounting evidence to suggest they offer a valuable pharmacoeconomic strategy to lower healthcare costs in patients with psoriasis. Furthermore, the introduction of biosimilars can increase the number of patients able to receive biologics, allowing these patients to be treated earlier in the disease course, potentially modifying the course of their disease and reducing the risk of comorbidities. In time, the emergence of additional data, particularly those related to long-term safety, efficacy in extrapolated indications and the effects of switching, should reassure physicians and help overcome the final hurdles for a wider implementation of biosimilars. This review aims to provide an overview of current treatment approaches for patients with moderate-to-severe psoriasis in the biosimilars era and explores both the current challenges and potential opportunities to improve access to high-quality, effective treatments.
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