1,721,260 research outputs found
Across Diagnostic Boundaries: Genetic Variants for Neuropsychiatric Disorders and their Association with Human Brain Structure
Full text linkWith the advances in genome-wide association studies (GWAS), hundreds of genetic variants have been identified for neuropsychiatric disorders. Strikingly, many of these genetic variants showed complex associations across diagnostic groups. For example, the second cross-disorder GWAS meta-analysis by the Psychiatric Genomics Consortium (Lee et al., 2019) identified 11 antagonistic single-nucleotide polymorphisms (SNPs) that were associated with an increased risk for one neuropsychiatric disorder, while being protective against another disorder. Furthermore, the cross-disorder GWAS meta-analysis uncovered 23 highly pleiotropic SNPs that were associated with at least four neuropsychiatric disorders and 22 SNPs that were predominantly associated with schizophrenia (SCZ) but not with the other disorders. The underlying molecular mechanisms by which these genetic variants alter the risk of distinct neuropsychiatric disorders are largely unclear. The present thesis conducted two imaging genetic studies to uncover the associations between antagonistic, highly pleiotropic, and predominantly SCZ-associated SNPs with brain structure and brain-related traits.
Study 1 performed a systematic characterization of the 11 antagonistic SNPs. Here, eight of the 11 antagonistic SNPs were significantly associated with at least one brain structural phenotype using the GWAS summary statistics from the ENIGMA and CHARGE consortia. Several of the implicated phenotypes were found to be altered in patients with bipolar disorder, major depression, or SCZ compared to controls. Six of the eight antagonistic SNPs were significantly associated with gene expression in brain tissue, and all eight antagonistic SNPs were significantly associated with cognitive-behavioral traits. Furthermore, rs301805 and rs1933802 were significantly associated with voxel-wise gray matter volume in data from the FOR2107 study.
Study 2 used data from the UK Biobank (n=28,952) to examine the association of a genetic risk score of highly pleiotropic SNPs (PleioPsych-GRS) and a genetic risk score of predominantly SCZ-associated SNPs (SCZ-GRS) with brain structure and outcomes related to mental health. To prioritize individual SNPs, the association of each SNP with brain structure was investigated. Study 2 found that the PleioPsych-GRS was not significantly associated with brain structural phenotypes after multiple testing corrections, whereas the SCZ-GRS was significantly associated with left and right putamen volume and left and right lateral orbitofrontal surface area, among others. The PleioPsych-GRS and the SCZ-GRS were significantly associated with eight and four outcomes related to mental health, respectively. Furthermore, two highly pleiotropic and ten predominantly SCZ-associated SNPs were significantly associated with at least one brain structural phenotype.
In conclusion, this thesis showed that antagonistic, predominantly SCZ-associated and, to a lesser extent, highly pleiotropic SNPs for neuropsychiatric disorders were associated with brain structure. In addition, the SNPs were associated with traits related to mental health, cognition, and behavior. These findings provided a notion of how these SNPs might influence disease development and led to the prioritization of selected SNPs and brain regions relevant for further investigations. Future work should extend these findings by exploring the association of these SNPs with additional brain modalities, including white matter microstructure and structural and functional connectivity of the human brain
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Contribution of common genetic variants to disease status and symptom dimensions in affective and psychotic disorders
Full text linkAffective and psychotic disorders, such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia spectrum disorders (SSD), represent complex psychiatric conditions with a moderate to high heritability. Throughout the last decade, genome-wide association studies (GWAS) have demonstrated the association of many common genetic variants with disease risk. However, the pathophysiological mechanisms of affective and psychotic disorders are still incompletely understood and it is expected that many more disease-associated genetic loci await identification. Moreover, while the different affective and psychotic disorders are considered distinct entities by current diagnostic systems, they exhibit notable phenotypic overlaps and substantial genetic correlations. This suggests that etiological processes may be partially shared between diagnostic groups. Against this backdrop, the three studies included in this thesis were conducted to improve our understanding of the role of common genetic variation in affective and psychotic disorders. In particular, in the first and second study, the contribution of common genetic variants to symptom dimensions of acute and lifetime psychopathology observed across MDD, BD, and SSD was examined. In the third study, the largest GWAS meta-analysis of BD to date was conducted, which revealed novel disease-associated loci and provided insights into the underlying pathobiology via a plethora of GWAS downstream analyses. Altogether, the results of this research expand our knowledge on the complex relationships of common genetic variants with disease status and symptom dimensions within and across affective and psychotic disorders
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study
No full textOBJECTIVES: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients. METHODS: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models. RESULTS: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment. CONCLUSIONS: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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