1,721,021 research outputs found
Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
No full textObjective
Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.
Design
We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.
Results
We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.
Conclusion
HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.http://dx.doi.org/10.13039/501100011747 Novo Nordisk Foundation Center for Basic Metabolic Researchhttp://dx.doi.org/10.13039/501100002301 Eesti Teadusagentuurhttp://dx.doi.org/10.13039/501100002428 Austrian Science FundEU H2020BigTempHealthhttp://dx.doi.org/10.13039/501100008530 European Regional Development Fundhttp://dx.doi.org/10.13039/501100001862 Svenska Forskningsrådet Formashttp://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/100000002 National Institutes of Healt
Inimese Per3 geeni tandeemse korduse koopiaarvu määramine teise põlvkonna sekveneerimisandmetest
Full text linkVarieeruva koopiaarvuga tandeemsed kordused on üle inimese genoomis laialt levinud. VNTRi (Variable Number of Tandem Repeats) perekonna moodustavad suur hulk erinevate pikkustega järjestusi. VNTRe on pikalt peetud rämps DNA-ks kuid järjest rohkem selgub nende mõju fenotüübile. Töös on lühiülevaade erinevatest programmidest, mida kasutatakse VNTR-ide leidmisel DNA järjestustest. Teise põlvkonna sekvneerimise levikuga ning täisgenoomide sekveneerimisega tekkis rida uusi võimalusi saada informatsiooni otse sekveneeritud andmetelt. Käesolevas bakalaureusetöös uurin Per3 geeni VNTR-i koopiaarvu määramist teise põlvkonna sekveneerimisandmete põhjal, võrdlen erinevaid metoodikaid k-meri katvuse leidmiseks ning nende kasutamiseks VNTR-ide määramisel. Genotüüpide võrdlemisel võtsin aluseks PCR metoodikaga määratud Per3 geeni polümorfismi rs57875989. Tulemustest lähtub, et GATK tööriista poolt määratud Per3 genotüüp on ebatäpne võrreldes agaroosgeeli või k-mer metoodikal saadud tulemusega. Kuigi antud töös toimunud k-mer metoodikaga genotüpiseerimine ei ole piisavalt suure täpsusega, on see hetkel üks väheseid kui mitte ainukesi sekveneeritud täisgenoomi andmete põhjal VNTR arvude määramise meetodeid
Une- ja ärkveloleku tsükli analüüs TÜ Eesti Geenivaramu doonoritel Per3 geeni varieeruva arvuga tandemkorduse rs57875989 mõju uneparameetritele
Full text linkÜlegenoomne assotsiatsiooniuuring une kestust määravate geneetiliste faktorite identifitseerimiseks Tartu Ülikooli Eesti Geenivaramu andmetel Une kestuse seos terviseseisunditega
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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
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
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