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- 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. |
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| 3. |
- 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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| 6. |
- 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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| 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. |
- 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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| 10. |
- 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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