| 1. |
- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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| 2. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 3. |
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| 4. |
- Jonsson, Lina, 1982, et al.
(författare)
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Rare and Common Variants Conferring Risk of Tooth Agenesis
- 2018
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Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 97:5, s. 515-522
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Tidskriftsartikel (refereegranskat)abstract
- We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.
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| 5. |
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| 6. |
- Skuladottir, AT, et al.
(författare)
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A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1598-
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Tidskriftsartikel (refereegranskat)abstract
- Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10−24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.
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| 7. |
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| 8. |
- Hreinsdottir, S., et al.
(författare)
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Volcanic plume height correlated with magma-pressure change at Grimsvotn Volcano, Iceland
- 2014
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 7:3, s. 214-218
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Tidskriftsartikel (refereegranskat)abstract
- Magma flow during volcanic eruptions causes surface deformation that can be used to constrain the location, geometry and internal pressure evolution of the underlying magmatic source(1). The height of the volcanic plumes during explosive eruptions also varies with magma flow rate, in a nonlinear way(2,3). In May 2011, an explosive eruption at Grimsvotn Volcano, Iceland, erupted about 0.27 km(3) dense-rock equivalent of basaltic magma in an eruption plume that was about 20 km high. Here we use Global Positioning System (GPS) and tilt data, measured before and during the eruption at Grimsvotn Volcano, to show that the rate of pressure change in an underlying magma chamber correlates with the height of the volcanic plume over the course of the eruption. We interpret ground deformation of the volcano, measured by geodesy, to result from a pressure drop within a magma chamber at about 1.7 km depth. We estimate the rate of magma discharge and the associated evolution of the plume height by differentiating the co-eruptive pressure drop with time. The time from the initiation of the pressure drop to the onset of the eruption was about 60 min, with about 25% of the total pressure change preceding the eruption. Near-real-time geodetic observations can thus be useful for both timely eruption warnings and for constraining the evolution of volcanic plumes.
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| 9. |
- Berg-Beckhoff, G., et al.
(författare)
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Political stringency, infection rates, and higher education students' adherence to government measures in the Nordic countries and the UK during the first wave of the COVID-19 outbreak
- 2022
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Ingår i: Preventive Medicine. - : Elsevier. - 0091-7435 .- 1096-0260. ; 164
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Tidskriftsartikel (refereegranskat)abstract
- Understanding predictors of adherence to governmental measures to prevent the spread of the COVID-19 is fundamental to guide health communication. This study examined whether political stringency and infection rates during the first wave of the pandemic were associated with higher education students' adherence to COVID-19 government measures in the Nordic countries (Denmark, Finland, Norway, Iceland, and Sweden) and the United Kingdom.Both individual- and country-level data were used in present study. An international cross-sectional subsample (n = 10,345) of higher-education students was conducted in May–June 2020 to collect individual-level information on socio-demographics, study information, living arrangements, health behaviors, stress, and COVID-19-related concerns, including adherence to government measures. Country-level data on political stringency from the Oxford COVID-19 Government Response Tracker and national infection rates were added to individual-level data. Multiple linear regression analyses stratified by country were conducted.Around 66% of students reported adhering to government measures, with the highest adherence in the UK (73%) followed by Iceland (72%), Denmark (69%), Norway (67%), Finland (64%) and Sweden (49%). Main predictors for higher adherence were older age, being female and being worried about getting infected with COVID-19 (individual-level), an increase in number of days since lockdown, political stringency, and information about COVID-19 mortality rates (country-level). However, incidence rate was an inconsistent predictor, which may be explained by imperfect data quality during the onset of the pandemic.We conclude that shorter lockdown periods and political stringency are associated with adherence to government measures among higher education students at the outset of the COVID-19 pandemic.
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| 10. |
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| 11. |
- Gisladottir, Rosa S, et al.
(författare)
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Sequence Variants in TAAR5 and Other Loci Affect Human Odor Perception and Naming.
- 2020
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Ingår i: Current biology : CB. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 30:23
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Tidskriftsartikel (refereegranskat)abstract
- Olfactory receptor (OR) genes in humans form a special class characterized by unusually high DNA sequence diversity, which should give rise to differences in perception and behavior. In the largest genome-wide association study to date based on olfactory testing, we investigated odor perception and naming with smell tasks performed by 9,122 Icelanders, with replication in a separate sample of 2,204 individuals. We discovered an association between a low-frequency missense variant in TAAR5 and reduced intensity rating of fish odor containing trimethylamine (p.Ser95Pro, pcombined= 5.6× 10-15). We demonstrate that TAAR5 genotype affects aversion to fish odor, reflected by linguistic descriptions of the odor and pleasantness ratings. We also discovered common sequence variants in two canonical olfactory receptor loci that associate with increased intensity and naming of licorice odor (trans-anethole: lead variant p.Lys233Asn in OR6C70, pcombined= 8.8× 10-16 and pcombined= 1.4× 10-9) and enhanced naming of cinnamon (trans-cinnamaldehyde; intergenic variant rs317787-T, pcombined= 5.0× 10-17). Together, our results show that TAAR5 genotype variation influences human odor responses and highlight that sequence diversity in canonical OR genes can lead to enhanced olfactory ability, in contrast to the view that greater tolerance for mutations in the human OR repertoire leads to diminished function.
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| 12. |
- Halvarsson, A, et al.
(författare)
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Long-term effects of a progressive and specific balance-training programme with multi-task exercises for older adults with osteoporosis: a randomized controlled study
- 2016
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Ingår i: Clinical rehabilitation. - : SAGE Publications. - 1477-0873 .- 0269-2155. ; 30:11, s. 1049-1059
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate long-term effects of balance-training on concerns about falling, gait, balance performance, and physical function in older adults with osteoporosis and increased risk of falling. Design: Randomized controlled trial, including three groups (training, training+physical activity, and control group), with follow-ups at three, nine, and 15 months. Short-term, three-month follow-up, benefits for those who fulfilled the first follow-up ( n = 69) have previously been reported. Setting: Stockholm, Sweden. Participants: A total of 96 elderly, age 66–87, with verified osteoporosis. Interventions: Balance-training programme including dual- and multitasks, with or without supplementary physical activity, three times/week over 12 weeks. Measurements: Concerns about falling Falls Efficacy Scale -International (FES-I), walking at preferred speed with and without a cognitive dual-task and at fast speed, balance tests (one-leg stance and modified figure-of-eight), and physical function Late-Life Function and Disability Instrument (LLFDI). Results: Participants in the training group maintained positive effects throughout the study period for concerns about falling (baseline vs. 15 months, median 27.5 vs. 23 points, p < 0.001) and walking performance (baseline vs. 15 months, p ⩽ 0.05 with an improvement of 0.9–1.4 m/s). The Training+physical activity group declined to baseline values at the nine-month follow-up, and were even lower at the 15-month follow-up for concerns about falling (median 26 vs. 26 points), walking performance (changes of −0.02 to 0.04 m/s), and physical function (mean 44.0 vs. 42.9 points). The control group remained unchanged throughout the study period. Conclusions: This balance-training programme reduced concerns about falling, and also improved gait in older adults with osteoporosis and increased risk of falling in a long-term perspective – important issues for fall prevention.
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| 13. |
- Halvarsson, A, et al.
(författare)
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Long-term effects of new progressive group balance training for elderly people with increased risk of falling - a randomized controlled trial
- 2013
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Ingår i: Clinical rehabilitation. - : SAGE Publications. - 1477-0873 .- 0269-2155. ; 27:5, s. 450-458
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the long-term effects of a progressive and specific balance group-based program in healthy elderly individuals with increased risk of falling. Design: Follow-up of a randomized controlled trial at nine and 15 months on a population that has previously been described at three months. Setting: The study was conducted in Stockholm, Sweden. Subjects: 59 community-dwelling elderly (age 67–93 years), recruited by advertisement, were randomly allocated to training or to serve as controls. Intervention: Group balance training three times per week during 12 weeks with a 15 month follow-up time. Main measures: Participants were assessed at baseline, three, nine, and 15 months thereafter for gait function (preferred and fast walking), rapid step execution (single and dual task), fear of falling, and likelihood of depression. Results: Fast gait speed ( p = 0.004), dual task step execution ( p = 0.006) and fear of falling ( p = 0.001) were still improved in the training group at nine months follow-up. Only self-perceived fear of falling remained significantly improved ( p = 0.012) at 15 months follow-up. Although fast gait speed had decreased to baseline level in the training group (1.49 m/s) it remained significantly higher than in the control group (1.37 m/s) at the end of the study, a difference between the groups that was not seen at baseline. Conclusion: This training program provided important positive short and long-term benefits to gait, balance function, and fear of falling.
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| 14. |
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| 19. |
- Andersson, Eva A., et al.
(författare)
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Physical activity for persons with obesity—a health project reported
- 2008
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Ingår i: Forum on Public Policy Online. - : Oxford Round Table. - 1938-9809. ; 4:Spring
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Tidskriftsartikel (refereegranskat)abstract
- In public health contexts, increased physical activity habits and fitness (aerobic and strength capacities) are positively related for promoting health and preventing and treating common diseases/problems, including obesity and overweight. A strongly graded inverse association between physical activity and obesity has been shown both for adults and children. However, a lower mortality risk has been shown for those with greater weight but good aerobic capacity than for those of recommended weight but less fit. On the basis of a health project with physical activity for persons with or without obesity, the paper discusses evidence-based methods for promoting physical activity. General guidelines for the amount of physical activity for persons are described, as are the numerous physiological and medical advantages of physical activity. The economic benefits are also illustrated. The paper exemplifies methods of measuring physical activity habits and physical fitness. These two factors must be observed when showing improvements in public-health contexts, including groups with obesity.
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| 20. |
- Andersson, Eva A., et al.
(författare)
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Äldre blir starkare av Hälsoprojektet
- 2013
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Ingår i: Svensk Idrottsforskning. - Stockholm : Centrum för idtrottsforskning (CIF). - 1103-4629. ; 22:1, s. 25-27
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- En god kondition och styrka har samband med förbättrad hälsa, minskad förekomst av flera folksjukdomar samt ökad livslängd. Fysiologiska tester kan vara stimulerande för äldre att följa utvecklingen av sin fysiska kapacitet och för olika aktörer som vill göra hälsoutvärderingar.
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| 21. |
- Bonnard, M, et al.
(författare)
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Different strategies to compensate for the effects of fatigue revealed by neuromuscular adaptation processes in humans.
- 1994
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Ingår i: Neuroscience Letters. - 0304-3940 .- 1872-7972. ; 166:1, s. 101-5
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Tidskriftsartikel (refereegranskat)abstract
- An initially submaximal hopping task was maintained with the same global power output until it became the maximal performance; since there was no decrease in performance, any change in behavior occurring with fatigue characterizes the strategies allowing to compensate for the effects of fatigue. In a prolonged hopping task, fatigue is likely to be most prominent in the ankle extensor muscles since they are the main contributors to vertical propulsion in the hop. With fatigue, all subjects landed with more flexed knees and with an increased activity in the biarticular rectus femoris muscle indicating some compensation between the knee and ankle joint. Furthermore, two different strategies appeared to further compensate for the important fatigue of the ankle extensor muscles: one was organized across joints and consisted in a heavier reliance of the knee extensor vastus lateralis, and the other was organized within the fatigued joint and consisted in an earlier preactivation of the gastrocnemius. As a consequence, two different adaptations of the ground reaction force profiles appeared at the end of the session; each being related to one of these two strategies.
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| 22. |
- Cresswell, A G, et al.
(författare)
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The influence of sudden perturbations on trunk muscle activity and intra-abdominal pressure while standing.
- 1994
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Ingår i: Experimental Brain Research. - 0014-4819 .- 1432-1106. ; 98:2, s. 336-41
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Tidskriftsartikel (refereegranskat)abstract
- Unexpected ventral and dorsal perturbations and expected, self-induced ventral perturbations were delivered to the trunk by suddenly loading a vest strapped to the torso. Six male subjects were measured for intra-abdominal pressure (IAP) and intra-muscular electromyography of the transversus abdominis (TrA), obliquus internus abdominis (OI), obliquus externus abdominis (OE) and rectus abdominis (RA) muscles. Erector spinae (ES) activity was recorded using surface electromyography. Displacements of the trunk and head were registered using a video-based system. Unexpected ventral loading produced activity in TrA, OI, OE and RA, and an IAP increase well in advance of activity from ES. Expected ventral loading produced pre-activation of all muscles and an increased IAP prior to the perturbation. The TrA was always the first muscle active in both the unexpected and self-loading conditions. Of the two ventral loading conditions, forward displacement of the trunk was significantly reduced during the self-loading. Unexpected dorsal loading produced coincident activation of TrA, OI, OE, RA and ES. These results indicate a response of the trunk muscles to sudden expected and unexpected ventral loadings other than the anticipated immediate extensor torque production through ES activation. It is suggested that the increase in IAP is a mechanism designed to improve the stability of the trunk through a stiffening of the whole segment.
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