Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Intergenerational continuity in attitudes toward reading and reading behavior

Students' reading preferences develop in social contexts, and parents shape such environments. Assuming a process of transmission across generations, we analyzed the role of mothers' attitudes toward reading and reading behavior. A sample of 380 ninth-grade students completed a questionnaire to assess their attitudes toward reading (with respect to utility and enjoyment) and to collect details about their extracurricular reading behavior. Mothers were interviewed and asked to provide comparable information about their own reading behavior and attitudes. Results showed substantial positive relations between mothers' and students' attitudes toward reading and reading behavior, although the effects were small in magnitude. Taken together, evenwhen children reach adolescence, socialization effects from parents can be found in the domain of reading

A Person Centered Approach for Analyzing the Development of Students’ Subject-Interests in Language Arts, Mathematics, and English as a Foreign Language From Grade 4 to 11

Forschungsarbeiten zur Interessensentwicklung konnten vielfach zeigen, dass Schülerinnen und Schüler mit undifferenziert hohen schulfachbezogenen Interessen in die Schule eintreten, die mittleren Interessen im weiteren Schulverlauf jedoch stetig absinken. Neuere Studien verweisen auf einen stagnierenden Interessensabfall ab Jahrgangsstufe 7 und einen leichten Interessensanstieg etwa ab Jahrgangsstufe 11. Gemäß dem Modell der Interessensdifferenzierung (Todt & Schreiber, 1998) lässt sich der mittlere Interessensabfall auf einen Differenzierungsprozess zurückführen: Die Schülerinnen und Schüler fokussieren ihr Interesse nach Schuleintritt auf einige wenige Fächer, während die übrigen Fachinteressen sinken. Anhand der Fachinteressen Deutsch, Mathematik und Englisch zu Jahrgangsstufe 4 bis 11 wurde untersucht, inwieweit sich derartige Differenzierungsprozesse über eine latente Klassenanalyse mit längsschnittlichen Daten (LCA) nachzeichnen lassen. Die Analyse von N = 293 Schülerinnen und Schülern bestätigte zunächst den Befund einer mittleren, kurvenlinearen Interessensentwicklung. Die LCA ergab fünf latente Klassen. Die Mittelwertdifferenzen der Fachinteressen ließen nur für zwei der fünf latenten Klassen eine zunehmende Interessensdifferenzierung zu Jahrgangsstufe 11 vermuten.Numerous studies showed that students enter the school system with high and undifferentiated interests. However, academic interests on average decrease during the school course. Recent findings point to a stagnancy of this negative development in grade 7 and a slight increase in grade 11. According to the model of interest differentiation (Todt & Schreiber, 1998) students’ decreasing academic interests can be traced back to a process of differentiation: Students focus their interests on a limited number of subjects whereas their interests for the remaining subjects decrease. Using students’ self-reports on their subject-interests in language arts, mathematics and English as a foreign language at grade 4 to grade 11 we analyzed whether (a) latent class(es) (latent class analysis with longitudinal data, LCA) of a differentiating interest profile can be found. On average the analysis of N = 293 students showed decreasing interests up to grade 7 and slightly increasing interests in grade 11. The LCA indicated five latent classes. Two of them revealed a pattern of interest differentiation in grade 11

Mechanisms mediating the relation between reading self-concept and reading comprehension

European Journal of Psychology of EducationReading self-concept is an important predictor of reading comprehension and vice versa. However, the mechanisms that are at work in this relation have yet to be identified. In line with the self-enhancement approach, we propose that in the reading domain, amount of reading, book choice (text difficulty and book length), and intrinsic reading motivation should function as mediating variables in the relation between reading self-concept and reading comprehension. We tested this hypothesis with longitudinal data gathered from N?=?405 German students in Grades 7, 8, and 9. The results showed that reading self-concept had a positive effect on reading comprehension, intrinsic motivation, book length, and amount of reading. However, indirect paths between reading self-concept and reading comprehension were found only for intrinsic motivation, not for amount of reading or book choice. The results are discussed in the context of students’ reading comprehension development, and consequences for research and education are derived

Vermittelnde Faktoren im Zusammenhang von Selbstkonzept und Kompetenz im Bereich Lesen

Tagung der Gesellschaft für Empirische Bildungsforschung (GEBF), Köln, 25.-27.02.201

Vermittelnde Faktoren im Zusammenhang von Selbstkonzept und Kompetenz im Bereich Lesen

Tagung der Gesellschaft für Empirische Bildungsforschung (GEBF), Köln, 25.-27.02.201

Does Vocational Training Boost Motivation? : A Comparison of the Development of Goal Orientation From Secondary to Upper Secondary Schools or Vocational Training

Bisherige Forschungsarbeiten zeigen, dass die Entwicklung von Zielorientierungen von kontextuellen Bedingungen abhängen kann. So wird beispielsweise ein Rückgang der Lernzielorientierung nach dem Übergang in die Sekundarstufe I berichtet (Anderman & Midgley, 1997). Schlechter werdende Passung zwischen Lernendem und Lernumgebung wird als mögliche Ursache für den Rückgang genannt. Im vorliegenden Beitrag wurde untersucht, ob und wie sich Zielorientierungen von Beginn der Sekundarstufe I bis nach dem Übergang in die Sekundarstufe II bzw. in das Ausbildungssystem entwickeln. Analysiert wurden Daten von N = 650 Schülerinnen und Schülern sowie Auszubildenden zu drei Messzeitpunkten (Klasse 5, Klasse 6, Stufe 11/1. Ausbildungsjahr). Die Ergebnisse latenter Neighbor-Change-Analysen zeigen in beiden Gruppen eine Abnahme der Annäherungs- und Vermeidungsleistungszielorientierung. Die Lernzielorientierung nimmt in beiden Gruppen zu, wobei der Anstieg für Auszubildende signifikant höher ausfällt. Die Ergebnisse erweisen sich unter Berücksichtigung der Kovariaten Geschlecht, Schulleistung, Migrationshintergrund und sozioökonomischer Status als robust. Die Ergebnisse werden vor dem Hintergrund der Stage-Environment-Fit-Theorie und Zielstrukturen diskutiert.Research has shown that the development of goal orientations also depends on contextual conditions. Anderman and Midgley (1997) reported a decline in mastery goal orientation after transition from elementary to secondary education. A possible explanation for this is the deteriorating fit between the learner and the learning environment. In this study, we analyzed whether and how students’ goal orientation develops between secondary school and the transition to upper secondary school or vocational training. Neighbor change analyses include data from N = 650 students and trainees at three measurement points (fifth, sixth, and eleventh grade/ first year of training). We found a decline in performance-approach and performance-avoidance goal orientation without any group differences. Mastery goal orientation increased in both groups, whereby the increase was significantly higher for trainees. When taking into account the covariates gender, school performance, migration background, and socioeconomic status, the effects remained stable. The results are discussed in the context of stage–environment fit theory and goal structures

The academic competence and self-concept of upper-track students with and without an upper-track school recommendation

Die vorliegende Studie widmet sich der Entwicklung schulischer Kompetenzen sowie der Entwicklung des Fähigkeitsselbstkonzepts von Gymnasiastinnen und Gymnasiasten mit und ohne gymnasiale Übergangsempfehlung. In Ergänzung werden ferner die Daten von Haupt- und Realschülerinnen und -schülern in die Betrachtung einbezogen. Die Analysen beziehen sich auf Daten der vierten bis siebten Klassenstufe aus der Bamberger Längsschnittstudie BiKS-8-14 („Bildungsprozesse, Kompetenzentwicklung und Selektionsentscheidungen im Vorschul und Schulalter“). Die Ergebnisse zeigen am Ende der siebten Klassenstufe deutliche Kompetenzunterschiede in den Bereichen Mathematik und Lesen zwischen Gymnasiastinnen und Gymnasiasten mit beziehungsweise ohne gymnasiale Schullaufbahnempfehlung. Auch scheinen mittlere Kompetenzunterschiede zwischen Klassenstufe 4 und 7 nicht abzunehmen. Für das Fähigkeitsselbstkonzept Mathematik sowie die Schulnoten in den Fächern Deutsch und Mathematik können am Ende der siebten Klassenstufe ebenso statistisch bedeutsame Unterschiede gezeigt werden. Die Ergebnisse werden diskutiert vor dem Hintergrund der Frage nach Kosten-/ Nutzenaspekten bestimmter Schulformentscheidungen.This paper compares the academic competence of upper-track students in secondary school who have an upper-track school recommendation with students who also attend upper-track schools but without an upper-track school recommendation. Additionally, non-academic track students are considered. We focused on two outcomes: students’ school competences and students’ self-concept. The analyses are based on data from fourth- and seventh-grade students in the BiKS-8-14 panel study. Results indicated substantial differences in mathematics and reading competence between students attending upper-track schools with and without an uppertrack school recommendation. Furthermore, there were no signs of a decreasing competence gap between grade 4 and grade 7. With regard to students’ self-concept in mathematics as well as German and mathematics grades at the end of grade 7, we also found significant differences between students with and without upper-track school recommendation. Our findings are discussed in light of the costs and benefits of attending different school tracks