| 1. |
- Wang, Z., et al.
(författare)
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Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
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Tidskriftsartikel (refereegranskat)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
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| 3. |
- Dwibedi, Chinmay, 1987, et al.
(författare)
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Effect of self-managed lifestyle treatment on glycemic control in patients with type 2 diabetes
- 2022
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Ingår i: npj Digital Medicine. - : Nature Research. - 2398-6352. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- The lack of effective, scalable solutions for lifestyle treatment is a global clinical problem, causing severe morbidity and mortality. We developed a method for lifestyle treatment that promotes self-reflection and iterative behavioral change, provided as a digital tool, and evaluated its effect in 370 patients with type 2 diabetes (ClinicalTrials.gov identifier: NCT04691973). Users of the tool had reduced blood glucose, both compared with randomized and matched controls (involving 158 and 204 users, respectively), as well as improved systolic blood pressure, body weight and insulin resistance. The improvement was sustained during the entire follow-up (average 730 days). A pathophysiological subgroup of obese insulin-resistant individuals had a pronounced glycemic response, enabling identification of those who would benefit in particular from lifestyle treatment. Natural language processing showed that the metabolic improvement was coupled with the self-reflective element of the tool. The treatment is cost-saving because of improved risk factor control for cardiovascular complications. The findings open an avenue for self-managed lifestyle treatment with long-term metabolic efficacy that is cost-saving and can reach large numbers of people. © 2022, The Author(s).
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| 4. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 5. |
- Zhao, J. H., et al.
(författare)
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Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets
- 2023
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Ingår i: Nature Immunology. - : Springer Nature. - 1529-2908 .- 1529-2916. ; 24:9, s. 1540-1551
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-alpha in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization. Here the authors identify genetic effectors of the level of inflammation-related plasma proteins and use Mendelian randomization to identify proteins that contribute to immune-mediated disease risk.
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| 6. |
- Cederberg, Matilda, et al.
(författare)
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Effects of a Person-Centered eHealth Intervention for Patients on Sick Leave Due to Common Mental Disorders (PROMISE Study): Open Randomized Controlled Trial
- 2022
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Ingår i: Jmir Mental Health. - : JMIR Publications Inc.. - 2368-7959. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sick leave due to common mental disorders (CMDs) is a public health problem in several countries, including Sweden. Given that symptom relief does not necessarily correspond to return to work, health care interventions focusing on factors that have proven important to influence the return to work process, such as self-efficacy, are warranted. Self-efficacy is also a central concept in person-centered care. Objective: The aim of this study is to evaluate the effects of a person-centered eHealth intervention for patients on sick leave due to CMDs. Methods: A randomized controlled trial of 209 patients allocated to either a control group (107/209, 51.2%) or an intervention group (102/209, 48.8%) was conducted. The control group received usual care, whereas the intervention group received usual care with the addition of a person-centered eHealth intervention. The intervention was built on person-centered care principles and consisted of telephone support and a web-based platform. The primary outcome was a composite score of changes in general self-efficacy (GSE) and level of sick leave at the 6-month follow-up. An intention-to-treat analysis included all participants, and a per-protocol analysis consisted of those using both the telephone support and the web-based platform. Results: At the 3-month follow-up, in the intention-to-treat analysis, more patients in the intervention group improved on the composite score than those in the control group (20/102, 19.6%, vs 10/107, 9.3%; odds ratio [OR] 2.37, 95% CI 1.05-5.34; P=.04). At the 6-month follow-up, the difference was no longer significant between the groups (31/100, 31%, vs 25/107, 23.4%; OR 1.47, 95% CI 0.80-2.73; P=.22). In the per-protocol analysis, a significant difference was observed between the intervention and control groups at the 3-month follow-up (18/85, 21.2%, vs 10/107, 9.3%; OR 2.6, 95% CI 1.13-6.00; P=.02) but not at 6 months (30/84, 35.7%, vs 25/107, 23.4%; OR 1.8, 95% CI 0.97-3.43; P=.06). Changes in GSE drove the effects in the composite score, but the intervention did not affect the level of sick leave. Conclusions: A person-centered eHealth intervention for patients on sick leave due to CMDs improved GSE but did not affect the level of sick leave.
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| 7. |
- Cederberg, Matilda, et al.
(författare)
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Person-centred eHealth intervention for patients on sick leave due to common mental disorders: study protocol of a randomised controlled trial and process evaluation (PROMISE)
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The number of people dealing with common mental disorders (CMDs) is a major concern in many countries, including Sweden. Sickness absence resulting from CMDs is often long-lasting and advancing return to work is a complex process impacted by several factors, among which self-efficacy appears to be an important personal resource. Person-centred care (PCC) has previously shown positive effects on self-efficacy however this needs to be further investigated in relation to patients with CMDs and in an eHealth context. METHODS AND ANALYSIS: This study is an open randomised controlled trial comparing a control group receiving standard care with an intervention group receiving standard care plus PCC by telephone and a digital platform. The primary outcome measure is a composite score of changes in sick leave and self-efficacy. Participants will include 220 primary care patients on sick leave due to CMDs and data will mainly be collected through questionnaires at baseline and 3, 6, 12 and 24 months from the inclusion date. Inclusion is ongoing and expected to be completed during the fall of 2020. A process and health economic evaluation will also be conducted. ETHICS AND DISSEMINATION: This study was approved by the Regional Ethical Review Board in Gothenburg, Sweden. Results will be published in peer-reviewed scientific journals and presented at national and international scientific conferences. This project is part of a broader research programme conducted at the Gothenburg Centre for Person-Centred Care (GPCC), where extensive work is undertaken to disseminate knowledge on and implementation of PCC. TRIAL REGISTRATION NUMBER: NCT03404583.
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| 10. |
- Kavaliunas, A, et al.
(författare)
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Importance of early treatment decisions on future income of multiple sclerosis patients
- 2020
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Ingår i: Multiple sclerosis journal - experimental, translational and clinical. - : SAGE Publications. - 2055-2173. ; 6:4, s. 2055217320959116-
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Tidskriftsartikel (refereegranskat)abstract
- Early initiation of disease-modifying treatment (DMT) is associated with better disability outcomes in multiple sclerosis (MS). However, little is known of how treatment decisions affect socio-economic outcomes. Objective To estimate the long-term impact of early initiation of DMT on the income of MS patients. Methods In total, 3610 MS patients were included in this register-based cohort study. We measured the association between the time to treatment and the outcome, defined as time from treatment initiation to a 95% decrease in annual earnings compared to each patient´s baseline level. Additionally, the association between time to treatment and increase of social benefits (sickness absence, disability pension) was investigated. A Cox model was adjusted for sex, onset age, education, family situation, country of birth, living area, and disability. Results MS patients initiating treatment later had a higher risk of reaching the outcome- those who started treatment after 2 years from MS onset lost 95% of their earnings sooner (HR, 1.19; 95% CI, 1.04–1.37). Furthermore, risk to receive an annual compensation of SEK 100,000 (≈EUR 10,500) was higher for the delayed treatment group. Conclusion Early treatment initiation in MS is associated with better socioeconomic outcome, adding to previous studies showing benefits regarding disability.
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