| 1. |
- Lekman, Magnus, et al.
(författare)
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A significant risk locus on 19q13 for bipolar disorder identified using a combined genome-wide linkage and copy number variation analysis
- 2015
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Ingår i: BioData Mining. - : Springer Science and Business Media LLC. - 1756-0381. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genetic background to bipolar disorder (BPD) has been attributed to different genetic and genomic risk factors. In the present study we hypothesized that inherited copy number variations (CNVs) contribute to susceptibility of BPD. We screened 637 BP-pedigrees from the NIMH Genetic Initiative and gave priority to 46 pedigrees. In this subsample we performed parametric and non-parametric genome-wide linkage analyses using similar to 21,000 SNP-markers. We developed an algorithm to test for linkage restricted to regions with CNVs that are shared within and across families. Results: For the combined CNV and linkage analysis, one region on 19q13 survived correction for multiple comparisons and replicates a previous BPD risk locus. The shared CNV map to the pregnancy-specific glycoprotein (PSG) gene, a gene-family not previously implicated in BPD etiology. Two SNPs in the shared CNV are likely transcription factor binding sites and are linked to expression of an F-box binding gene, a key regulator of neuronal pathways suggested to be involved in BPD etiology. Conclusions: Our CNV-weighted linkage approach identifies a risk locus for BPD on 19q13 and forms a useful tool to future studies to unravel part of the genetic vulnerability to BPD.
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| 2. |
- Kudra, Marina, 1992, et al.
(författare)
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Robust Preparation of Wigner-Negative States with Optimized SNAP-Displacement Sequences
- 2022
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Ingår i: PRX Quantum. - : AMER PHYSICAL SOC. - 2691-3399. ; 3:3
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Tidskriftsartikel (refereegranskat)abstract
- Hosting nonclassical states of light in three-dimensional microwave cavities has emerged as a promising paradigm for continuous-variable quantum information processing. Here we experimentally demonstrate high-fidelity generation of a range of Wigner-negative states useful for quantum computation, such as Schrodinger-cat states, binomial states, Gottesman-Kitaev-Preskill states, as well as cubic phase states. The latter states have been long sought after in quantum optics and have never been achieved experimentally before. We use a sequence of interleaved selective number-dependent arbitrary phase (SNAP) gates and displacements. We optimize the state preparation in two steps. First we use a gradient-descent algorithm to optimize the parameters of the SNAP and displacement gates. Then we optimize the envelope of the pulses implementing the SNAP gates. Our results show that this way of creating highly nonclassical states in a harmonic oscillator is robust to fluctuations of the system parameters such as the qubit frequency and the dispersive shift.
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| 3. |
- Andrén, Margareta, et al.
(författare)
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Coupling between mineral reactions, chemical changes in groundwater, and earthquakes in Iceland
- 2016
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Ingår i: Journal of Geophysical Research - Solid Earth. - 2169-9313 .- 2169-9356. ; 121:4, s. 2315-2337
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Tidskriftsartikel (refereegranskat)abstract
- Chemical analysis of groundwater samples collected from a borehole at Hafralækur, northernIceland, from October 2008 to June 2015 revealed (1) a long-term decrease in concentration of Si and Naand (2) an abrupt increase in concentration of Na before each of two consecutive M > 5 earthquakes whichoccurred in 2012 and 2013, both 76 km from Hafralækur. Based on a geochemical (major elements and stableisotopes), petrological, and mineralogical study of drill cuttings taken from an adjacent borehole, we areable to show that (1) the long-term decrease in concentration of Si and Na was caused by constant volumereplacement of labradorite by analcime coupled with precipitation of zeolites in vesicles and along fracturesand (2) the abrupt increase of Na concentration before the first earthquake records a switchover tononstoichiometric dissolution of analcime with preferential release of Na into groundwater. We attributedecay of the Na peaks, which followed and coincided with each earthquake to uptake of Na along fracturedor porous boundaries between labradorite and analcime crystals. Possible causes of these Na peaks are anincrease of reactive surface area caused by fracturing or a shift from chemical equilibrium caused by mixingbetween groundwater components. Both could have been triggered by preseismic dilation, which was alsoinferred in a previous study by Skelton et al. (2014). The mechanism behind preseismic dilation so far from thefocus of an earthquake remains unknown.
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| 4. |
- Tunón, Håkan, et al.
(författare)
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Forskare: Skapa inte mer polarisering mellan människa och natur, Moderaterna
- 2024
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Ingår i: Alltinget.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Viljan att skydda växter och djur får ibland orimliga effekter. Det skriver flera företrädare för Moderaternas arbetsgrupp för en kommande miljöpolitik på DN debatt.Farlig polariseringDe tar bland annat upp viktiga frågor om ”människans plats i naturen”. Men konflikten mellan utveckling och miljö är en återkommande missuppfattning. Frågan om naturvården främst bör utgå från människans eller naturens behov bidrar till en farlig polarisering. I själva verket är vi beroende av biologisk mångfald för mat, energi, kläder, byggnadsmaterial, rent vatten, fungerande jordbruksmark, ren luft, skydd mot epidemier, pandemier, andra katastrofer och framtida läkemedel.
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| 5. |
- Åkesson, Julia, et al.
(författare)
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Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression. Lower levels of neurofilament light chain (NfL) in CSF is superior in predicting the absence of disease activity two years after sampling (replication AUC = 0.77) compared to all other tested proteins. Importantly, we also identify a combination of 11 CSF proteins (CXCL13, LTA, FCN2, ICAM3, LY9, SLAMF7, TYMP, CHI3L1, FYB1, TNFRSF1B and NfL) that predict the severity of disability worsening according to the normalized age-related MS severity score (replication AUC = 0.90). The identification of these proteins may help elucidate pathogenetic processes and might aid decisions on treatment strategies for persons with MS.
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| 6. |
- Gustafsson, Mika, et al.
(författare)
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A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases
- 2015
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:313
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Tidskriftsartikel (refereegranskat)abstract
- Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.
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| 7. |
- Hössjer, Ola, et al.
(författare)
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Quantifying and estimating additive measures of interaction from case-control data
- 2017
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Ingår i: Modern stochastics: theory and applications. - 2351-6054. ; 4:2, s. 109-125
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we develop a general framework for quantifying how binary risk factors jointly influence a binary outcome. Our key result is an additive expansion of odds ratios as a sum of marginal effects and interaction terms of varying order. These odds ratio expansions are used for estimating the excess odds ratio, attributable proportion and synergy index for a case-control dataset by means of maximum likelihood from a logistic regression model. The confidence intervals associated with these estimates of joint effects and interaction of risk factors rely on the delta method. Our methodology is illustrated with a large Nordic meta dataset for multiple sclerosis. It combines four studies, with a total of 6265 cases and 8401 controls. It has three risk factors (smoking and two genetic factors) and a number of other confounding variables.
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| 8. |
- James, Tojo, et al.
(författare)
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Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients
- 2018
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:5, s. 912-928
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Tidskriftsartikel (refereegranskat)abstract
- Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as multiple sclerosis (MS). As a large proportion of expression quantitative trait loci (eQTLs) are context-specific, we performed RNA-Seq in peripheral blood mononuclear cells from MS patients (n = 145) to identify eQTLs in regions centered on 109 MS risk single nucleotide polymorphisms and 7 associated human leukocyte antigen variants. We identified 77 statistically significant eQTL associations, including pseudogenes and non-coding RNAs. Thirty-eight out of 40 testable eQTL effects were colocalized with the disease association signal. As many eQTLs are tissue specific, we aimed to detail their significance in different cell types. Approximately 70% of the eQTLs were replicated and characterized in at least one major peripheral blood mononuclear cell-derived cell type. Furthermore, 40% of eQTLs were found to be more pronounced in MS patients compared with non-inflammatory neurological diseases patients. In addition, we found two single nucleotide polymorphisms to be significantly associated with the proportions of three different cell types. Mapping to enhancer histone marks and predicted transcription factor binding sites added additional functional evidence for eight eQTL regions. As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. This study provides many novel and validated targets for future functional characterization of MS and other diseases.
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| 9. |
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| 10. |
- Lekman, Magnus, et al.
(författare)
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The genetic interacting landscape of 63 candidate genes in Major Depressive Disorder : an explorative study
- 2014
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Ingår i: BioData Mining. - : Springer Science and Business Media LLC. - 1756-0381. ; 7, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genetic contributions to major depressive disorder (MDD) are thought to result from multiple genes interacting with each other. Different procedures have been proposed to detect such interactions. Which approach is best for explaining the risk of developing disease is unclear. This study sought to elucidate the genetic interaction landscape in candidate genes for MDD by conducting a SNP-SNP interaction analysis using an exhaustive search through 3,704 SNP-markers in 1,732 cases and 1,783 controls provided from the GAIN MDD study. We used three different methods to detect interactions, two logistic regressions models (multiplicative and additive) and one data mining and machine learning (MDR) approach. Results: Although none of the interaction survived correction for multiple comparisons, the results provide important information for future genetic interaction studies in complex disorders. Among the 0.5% most significant observations, none had been reported previously for risk to MDD. Within this group of interactions, less than 0.03% would have been detectable based on main effect approach or an a priori algorithm. We evaluated correlations among the three different models and conclude that all three algorithms detected the same interactions to a low degree. Although the top interactions had a surprisingly large effect size for MDD (e. g. additive dominant model P-uncorrected = 9.10E-9 with attributable proportion (AP) value = 0.58 and multiplicative recessive model with P-uncorrected = 6.95E-5 with odds ratio (OR estimated from beta 3) value = 4.99) the area under the curve (AUC) estimates were low (< 0.54). Moreover, the population attributable fraction (PAF) estimates were also low (< 0.15). Conclusions: We conclude that the top interactions on their own did not explain much of the genetic variance of MDD. The different statistical interaction methods we used in the present study did not identify the same pairs of interacting markers. Genetic interaction studies may uncover previously unsuspected effects that could provide novel insights into MDD risk, but much larger sample sizes are needed before this strategy can be powerfully applied.
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