Welcome to Hirsla, Landspítali University Hospital research archive

Hirsla is an open access repository, designed as a place to store, index, preserve and redistribute in digital format scholarly work of Landspitali employees. (A/H1N1)

  • Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort.

    Heaney, Liam G; Perez de Llano, Luis; Al-Ahmad, Mona; Backer, Vibeke; Busby, John; Canonica, Giorgio Walter; Christoff, George C; Cosio, Borja G; FitzGerald, J Mark; Heffler, Enrico; et al. (Elsevier, 2021-04-19)
    One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy.
  • Genetic propensities for verbal and spatial ability have opposite effects on body mass index and risk of schizophrenia

    Jonsdottir, Gudrun A.; Einarsson, Gudmundur; Thorleifsson, Gudmar; Magnusson, Sigurdur H.; Gunnarsson, Arni F.; Frigge, Michael L.; Gisladottir, Rosa S.; Unnsteinsdottir, Unnur; Gunnarsson, Bjarni; Walters, G. Bragi; et al. (Elsevier, 2021-09-01)
    We generated two polygenic scores, one capturing verbal and the other spatial aspects of cognitive ability, using UK Biobank data and studied their effects on various diseases and other traits in the Icelandic population. The score tagging spatial ability associated with higher body mass index (β = 0.032, p = 3.2 × 10−13), but lower risk of schizophrenia (OR = 0.82, p = 8.8 × 10−9) and other mental disorders. Furthermore, it associated with less openness, a personality trait reflecting curiosity and creativity (β = −0.023, p = 1.3 × 10−4). Conversely, the score tagging verbal ability associated with lower body mass index (β = −0.023, p = 1.6 × 10−7) and more openness (β = 0.045, p = 3.5 × 10−14), but did not associate with risk of schizophrenia (OR = 0.97, p = 0.42). Furthermore, applying genomic structural equation modeling, we observed that the genetic component of verbal ability associated positively with the genetic component of schizophrenia after conditioning on the g factor (bg = 0.193, p = 5.4 × 10−4). Thus, at the genetic level, verbal and spatial ability exhibit contrasting associations with indicators of mental and physical health, as well as with personality.
  • A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease.

    Wightman, Douglas P; Jansen, Iris E; Savage, Jeanne E; Shadrin, Alexey A; Bahrami, Shahram; Holland, Dominic; Rongve, Arvid; Børte, Sigrid; Winsvold, Bendik S; Drange, Ole Kristian; et al. (Nature Publishing Group, 2021-09-07)
    Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.
  • Can ultrasound on admission in active labor predict labor duration and a spontaneous delivery?

    Hjartardóttir, Hulda; Lund, Sigrún H; Benediktsdóttir, Sigurlaug; Geirsson, Reynir T; Eggebø, Torbjørn M; 1Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavík, Iceland (Drs Hjartardóttir, Benediktsdóttir, and Geirsson); Faculty of Medicine, University of Iceland, Reykjavík, Iceland (Drs Hjartardóttir, Benediktsdóttir, and Geirsson). Electronic address: huldahja@landspitali.is. 2deCODE genetics, Reykjavík, Iceland (Dr Lund). 3Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavík, Iceland (Drs Hjartardóttir, Benediktsdóttir, and Geirsson); Faculty of Medicine, University of Iceland, Reykjavík, Iceland (Drs Hjartardóttir, Benediktsdóttir, and Geirsson). 4National Center for Fetal Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway (Dr Eggebø); Department of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger, Norway (Dr Eggebø); Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway (Dr Eggebø). (Elsevier, 2021-04-23)
    Background: Identifying predictive factors for a normal outcome at admission in the labor ward would be of value for planning labor care, timing interventions, and preventing labor dystocia. Clinical assessments of fetal head station and position at the start of labor have some predictive value, but the value of ultrasound methods for this purpose has not been investigated. Studies using transperineal ultrasound before labor onset show possibilities of using these methods to predict outcomes. Objective: This study aimed to investigate whether ultrasound measurements during the first examination in the active phase of labor were associated with the duration of labor phases and the need for operative delivery. Study design: This was a secondary analysis of a prospective cohort study at Landspitali University Hospital, Reykjavík, Iceland. Nulliparous women at ≥37 weeks' gestation with a single fetus in cephalic presentation and in active spontaneous labor were eligible for the study. The recruitment period was from January 2016 to April 2018. Women were examined by a midwife on admission and included in the study if they were in active labor, which was defined as regular contractions with a fully effaced cervix, dilatation of ≥4 cm. An ultrasound examination was performed by a separate examiner within 15 minutes; both examiners were blinded to the other's results. Transabdominal and transperineal ultrasound examinations were used to assess fetal head position, cervical dilatation, and fetal head station, expressed as head-perineum distance and angle of progression. Duration of labor was estimated as the hazard ratio for spontaneous delivery using Kaplan-Meier curves and Cox regression analysis. The hazard ratios were adjusted for maternal age and body mass index. The associations between study parameters and mode of delivery were evaluated using receiver operating characteristic curves. Results: Median times to spontaneous delivery were 490 minutes for a head-perineum distance of ≤45 mm and 682 minutes for a head-perineum distance of >45 mm (log-rank test, P=.009; adjusted hazard ratio for a shorter head-perineum distance, 1.47 [95% confidence interval, 0.83-2.60]). The median durations were 506 minutes for an angle of progression of ≥93° and 732 minutes for an angle of progression of <93° (log-rank test, P=.008; adjusted hazard ratio, 2.07 [95% confidence interval, 1.15-3.72]). The median times to delivery were 506 minutes for nonocciput posterior positions and 677 minutes for occiput posterior positions (log-rank test, P=.07; adjusted hazard ratio, 1.52 [95% confidence interval, 0.96-2.38]) Median times to delivery were 429 minutes for a dilatation of ≥6 cm and 704 minutes for a dilatation of 4 to 5 cm (log-rank test, P=.002; adjusted hazard ratio, 3.11 [95% confidence interval, 1.68-5.77]). Overall, there were 75 spontaneous deliveries; among those deliveries, 16 were instrumental vaginal deliveries (1 forceps delivery and 15 ventouse deliveries), and 8 were cesarean deliveries. Head-perineum distance and angle of progression were associated with a spontaneous delivery with area under the receiver operating characteristic curves of 0.68 (95% confidence interval, 0.55-0.80) and 0.67 (95% confidence interval, 0.55-0.80), respectively. Ultrasound measurement of cervical dilatation or position at inclusion was not significantly associated with spontaneous delivery. Conclusion: Ultrasound examinations showed that fetal head station and cervical dilatation were associated with the duration of labor; however, measurements of fetal head station were the variables best associated with operative deliveries. Keywords: angle of progression; delivery time; fetal head station; head-perineum distance; labor; transperineal ultrasound.
  • Leveraging the Mendelian disorders of the epigenetic machinery to systematically map functional epigenetic variation.

    Luperchio, Teresa Romeo; Boukas, Leandros; Zhang, Li; Pilarowski, Genay; Jiang, Jenny; Kalinousky, Allison; Hansen, Kasper D; Bjornsson, Hans T; 1Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States. 2Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States. 3Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 4Landspitali University Hospital, Reykjavik, Iceland. #Contributed equally. (eLife Sciences Publications, 2021-08-31)
    Although each Mendelian Disorder of the Epigenetic Machinery (MDEM) has a different causative gene, there are shared disease manifestations. We hypothesize that this phenotypic convergence is a consequence of shared epigenetic alterations. To identify such shared alterations, we interrogate chromatin (ATAC-seq) and expression (RNA-seq) states in B cells from three MDEM mouse models (Kabuki [KS] type 1 and 2 and Rubinstein-Taybi type 1 [RT1] syndromes). We develop a new approach for the overlap analysis and find extensive overlap primarily localized in gene promoters. We show that disruption of chromatin accessibility at promoters often disrupts downstream gene expression, and identify 587 loci and 264 genes with shared disruption across all three MDEMs. Subtle expression alterations of multiple, IgA-relevant genes, collectively contribute to IgA deficiency in KS1 and RT1, but not in KS2. We propose that the joint study of MDEMs offers a principled approach for systematically mapping functional epigenetic variation in mammals. Keywords: IgA deficiency; Mendelian; chromatin; computational biology; computational methods; epigenetics; genetics; genomics; histone machinery; mouse; systems biology.

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