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1.
  • Momozawa, Y, et al. (author)
  • IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
  • 2018
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
  • Journal article (peer-reviewed)abstract
    • GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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  • Bakken, TE, et al. (author)
  • Comparative cellular analysis of motor cortex in human, marmoset and mouse
  • 2021
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
  • Journal article (peer-reviewed)abstract
    • The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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7.
  • Sjöberg, Karin, et al. (author)
  • Multi-decadal surface ozone trends at globally distributed remote locations.
  • 2020
  • In: Elementa. - : University of California Press. - 2325-1026. ; 8:23
  • Journal article (peer-reviewed)abstract
    • Extracting globally representative trend information from lower tropospheric ozone observations is extremely difficult due to the highly variable distribution and interannual variability of ozone, and the ongoing shift of ozone precursor emissions from high latitudes to low latitudes. Here we report surface ozone trends at 27 globally distributed remote locations (20 in the Northern Hemisphere, 7 in the Southern Hemisphere), focusing on continuous time series that extend from the present back to at least 1995. While these sites are only representative of less than 25% of the global surface area, this analysis provides a range of regional long-term ozone trends for the evaluation of global chemistry-climate models. Trends are based on monthly mean ozone anomalies, and all sites have at least 20 years of data, which improves the likelihood that a robust trend value is due to changes in ozone precursor emissions and/or forced climate change rather than naturally occurring climate variability. Since 1995, the Northern Hemisphere sites are nearly evenly split between positive and negative ozone trends, while 5 of 7 Southern Hemisphere sites have positive trends. Positive trends are in the range of 0.5–2 ppbv decade–1, with ozone increasing at Mauna Loa by roughly 50% since the late 1950s. Two high elevation Alpine sites, discussed by previous assessments, exhibit decreasing ozone trends in contrast to the positive trend observed by IAGOS commercial aircraft in the European lower free-troposphere. The Alpine sites frequently sample polluted European boundary layer air, especially in summer, and can only be representative of lower free tropospheric ozone if the data are carefully filtered to avoid boundary layer air. The highly variable ozone trends at these 27 surface sites are not necessarily indicative of free tropospheric trends, which have been overwhelmingly positive since the mid-1990s, as shown by recent studies of ozonesonde and aircraft observations.
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  • Spain, S E, et al. (author)
  • The relationship between psychopathic features, violence and treatment outcome : The comparison of three youth measures of psychopathic features
  • 2004
  • In: Behavioral sciences & the law (Print). - : Wiley. - 0735-3936 .- 1099-0798. ; 22:1, s. 85-102
  • Journal article (peer-reviewed)abstract
    • Few studies have compared self-report and clinician-administered measures of youth psychopathic features in juvenile-justice settings in terms of antisocial behavior and treatment indices. In a sample of 85 adjudicated delinquents, the predictive validities of the Antisocial Process Screening Device (APSD), the modified Childhood Psychopathy Scale (mCPS), and the Hare Psychopathy Checklist: Youth Version (PCL:YV) were tested. Three indices of institutional antisocial behavior (physical aggression; verbal aggression; administrative infractions) and two indices of treatment progress (time to treatment level promotion; whether treatment levels were dropped) were used as external correlates. The self-report measures (mCPS more so than APSD) were more consistently and strongly related to antisocial behavior and to the days required to progress in treatment than the PCL:YV. The following issues are discussed: (i) implications of the potential impact of measurement format on the understanding and predictive validity of youth psychopathy features and measures; (ii) the differential predictive validity of self-report versus clinician-administered measures; and (iii) the potential practical utility of measures of psychopathic features in youth. Copyright (C) 2004 John Wiley Sons, Ltd.
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10.
  • Silberzahn, Raphael, et al. (author)
  • Many analysts, one dataset : Making transparent how variations in analytical choices affect results
  • 2018
  • In: Advances in Methods and Practices in Psychological Science. - : Sage Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 337-356
  • Journal article (peer-reviewed)abstract
    • Twenty-nine teams involving 61 analysts used the same dataset to address the same research question: whether soccer referees are more likely to give red cards to dark skin toned players than light skin toned players. Analytic approaches varied widely across teams, and estimated effect sizes ranged from 0.89 to 2.93 in odds ratio units, with a median of 1.31. Twenty teams (69%) found a statistically significant positive effect and nine teams (31%) observed a non-significant relationship. Overall 29 differentanalyses used 21 unique combinations of covariates. We found that neither analysts' prior beliefs about the effect, nor their level of expertise, nor peer-reviewed quality of analysis readily explained variation in analysis outcomes. This suggests that significant variation in the results of analyses of complex data may be difficult to avoid, even by experts with honest intentions. Crowdsourcing data analysis, a strategy by which numerous research teams are recruited to simultaneously investigate the same research question, makes transparent how defensible, yet subjective analytic choices influence research results.
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