| 1. |
- Kanai, M, et al.
(författare)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
- Butler-Laporte, G, et al.
(författare)
-
Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative
- 2022
-
Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 18:11, s. e1010367-
-
Tidskriftsartikel (refereegranskat)abstract
- Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.
|
|
| 3. |
|
|
| 4. |
- Matuozzo, D, et al.
(författare)
-
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
-
Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
|
|
| 5. |
- Matuozzo, Daniela, et al.
(författare)
-
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
- 2023
-
Ingår i: Genome medicine. - 1756-994X. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in~80% of cases.We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1×10-4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1×10-4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4×10-3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7×10-8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68×10-5).Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60years old.
|
|
| 6. |
- Almeida, David M., et al.
(författare)
-
Everyday stress components and physical activity : examining reactivity, recovery and pileup
- 2020
-
Ingår i: Journal of behavioral medicine. - : Springer. - 0160-7715 .- 1573-3521. ; 43:1, s. 108-120
-
Tidskriftsartikel (refereegranskat)abstract
- The experience of naturally-occurring stress in daily life has been linked with lower physical activity levels. However, most of this evidence comes from general and static reports of stress. Less is known how different temporal components of everyday stress interfere with physical activity. In a coordinated secondary analysis of data from two studies of adults, we used intensive, micro-longitudinal assessments (ecological momentary assessments, EMA) to investigate how distinct components of everyday stress, that is, reactivity to stressor events, recovery from stressor events, and pileup of stressor events and responses predict physical activity. Results showed that components of everyday stress predicted subsequent physical activity especially for indicators of stress pileup. In both studies, the accumulation of stress responses over the previous 12 h was more predictive of subsequent physical activity than current stress reactivity or recovery responses. Results are compared to the effects of general measures of perceived stress that showed an opposite pattern of results. The novel everyday stress approach used here may be fruitful for generating new insights into physical activity specifically and health behaviors in general.
|
|
| 7. |
- Cucuzzella, M., et al.
(författare)
-
Distributed Control of DC Grids : Integrating Prosumers' Motives
- 2022
-
Ingår i: IEEE Transactions on Power Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 0885-8950 .- 1558-0679. ; 37:4, s. 3299-3310
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, a novel distributed control strategy addressing a (feasible) psycho-social-physical welfare problem in islanded Direct Current (DC) smart grids is proposed. Firstly, we formulate a (convex) optimization problem that allows prosumers to share current with each other, taking into account the technical and physical aspects and constraints of the grid (e.g., stability, safety), as well as psycho-social factors (i.e., prosumers' personal values). Secondly, we design a controller whose (unforced) dynamics represent the continuous time primal-dual dynamics of the considered optimization problem. Thirdly, a passive interconnection between the physical grid and the controller is presented. Global asymptotic convergence of the closed-loop system to the desired steady-state is proved and simulations based on collected data on psycho-social aspects illustrate and confirm the theoretical results.
|
|
| 8. |
- Scott, Stacey B., et al.
(författare)
-
A Coordinated Analysis of Variance in Affect in Daily Life
- 2020
-
Ingår i: Assessment. - : Sage Publications. - 1073-1911 .- 1552-3489. ; 27:8, s. 1683-1698
-
Tidskriftsartikel (refereegranskat)abstract
- Despite widespread interest in variance in affect, basic questions remain pertaining to the relative proportions of between-person and within-person variance, the contribution of days and moments, and the reliability of these estimates. We addressed these questions by decomposing negative affect and positive affect variance across three levels (person, day, moment), and calculating reliability using a coordinated analysis of seven daily diary, ecological momentary assessment (EMA), and diary-EMA hybrid studies (across studies age = 18-84 years, totalN(persons)= 2,103, totalN(observations)= 45,065). Across studies, within-person variance was sizeable (negative affect: 45% to 66%, positive affect: 25% to 74%); in EMA more within-person variance was attributable to momentary rather than daily level. Reliability was adequate to high at all levels of analysis (within-person: .73-.91; between-person: .96-1.00) despite different items and designs. We discuss the implications of these results for the design of future intensive studies of affect variance.
|
|
| 9. |
- Smyth, Joshua M., et al.
(författare)
-
Computing Components of Everyday Stress Responses : Exploring Conceptual Challenges and New Opportunities
- 2023
-
Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 18:1, s. 110-124
-
Tidskriftsartikel (refereegranskat)abstract
- Repeated assessments in everyday life enables collecting ecologically valid data on dynamic, within-persons processes. These methods have widespread utility and application and have been extensively used for the study of stressors and stress responses. Enhanced conceptual sophistication of characterizing intraindividual stress responses in everyday life would help advance the field. This article provides a pragmatic overview of approaches, opportunities, and challenges when intensive ambulatory methods are applied to study everyday stress responses in "real time." We distinguish between three stress-response components (i.e., reactivity, recovery, and pileup) and focus on several fundamental questions: (a) What is the appropriate stress-free resting state (or "baseline") for an individual in everyday life? (b) How does one index the magnitude of the initial response to a stressor (reactivity)? (c) Following a stressor, how can recovery be identified (e.g., when the stress response has completed)? and (d) Because stressors may not occur in isolation, how can one capture the temporal clustering of stressors and/or stress responses (pileup)? We also present initial ideas on applying this approach to intervention research. Although we focus on stress responses, these issues may inform many other dynamic intraindividual constructs and behaviors (e.g., physical activity, physiological processes, other subjective states) captured in ambulatory assessment.
|
|
| 10. |
|
|
