Vergleichende Sprachbiographieforschung: Migrationsbedingte Brüche in unmittelbarer, erinnerter und vererbter Migration

Migrationsbedingte „Brüche“, die teilweise indirekt und teilweise direkt geäußert werden, stellen ein häufig wiederkehrendes Thema in der Analyse von Sprachbiographien dar. Der Beitrag verortet zunächst die Untersuchung sprachbiographischer Interviews im Kontext der Migrationslinguistik, sodass die Prozesse des Sprachgebrauchs aus sprecherindividueller Perspektive im Zentrum stehen. Anhand sprachbiographischer Interviewauszüge wird anschließend verdeutlicht, dass sprachbiographische Brüche in der Migration in unterschiedlichen Formen auftreten und dass sie sowohl als unmittelbar erlebte als auch als erinnerte oder von der Elterngeneration vermittelte Ereignisse von sprachbiographischer Bedeutung sind. Analysiert werden Beispiele unterschiedlicher Erhebungen mit jungen Geflüchteten aus Iran, Afghanistan und Syrien sowie Sprecherinnen und Sprechern mit türkischem, bosnischem und irakischem Migrationshintergrund. Durch die Gegenüberstellung von Migrationserfahrungen und den darin enthaltenen sprachbiographischen Brüchen können individuelle und gesellschaftliche Muster deutlich werden, die sich auf den Verlauf von Migration und Inklusion sowie auf Spracherwerb und Spracherhalt auswirken. Keywords: Mehrsprachigkeit, Migration, Flucht, Biographi

Genome-wide association study of panic disorder reveals geneticoverlap with neuroticism and depression

Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. Thecontributory genetic variants remainlargely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide associationstudy (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden).Standard GWAS quality control procedureswere conducted on each individual dataset, and imputation was performed using the 1000Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locuswas identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%).Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was28.0–34.2%. After correction for multiple testing, a significant genetic correlation was foundbetween PD and major depressivedisorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) withp<1×10−4werefollowed up in an independent sample of 2408 PD patients and 228,470controls from Denmark, Iceland and the Netherlands. In thecombined analysis, SNP rs144783209 showed the strongest association with PD (pcomb=3.10 × 10−7). Sign tests revealed asignificant enrichment of SNPs with a discoveryp-value of <0.0001 in the combined follow up cohort (p=0.048). The presentintegrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD

Genome-wide association study of panic disorder reveals geneticoverlap with neuroticism and depression

Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. Thecontributory genetic variants remainlargely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide associationstudy (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden).Standard GWAS quality control procedureswere conducted on each individual dataset, and imputation was performed using the 1000Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locuswas identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%).Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was28.0–34.2%. After correction for multiple testing, a significant genetic correlation was foundbetween PD and major depressivedisorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) withp<1×10−4werefollowed up in an independent sample of 2408 PD patients and 228,470controls from Denmark, Iceland and the Netherlands. In thecombined analysis, SNP rs144783209 showed the strongest association with PD (pcomb=3.10 × 10−7). Sign tests revealed asignificant enrichment of SNPs with a discoveryp-value of <0.0001 in the combined follow up cohort (p=0.048). The presentintegrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD

Early rhythm-control therapy in patients with atrial fibrillation

BACKGROUND Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk. METHODS In this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed ≤1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control included treatment with antiarrhythmic drugs or atrial fibrillation ablation after randomization. Usual care limited rhythm control to the management of atrial fibrillation–related symptoms. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome; the second primary outcome was the number of nights spent in the hospital per year. The primary safety outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. Secondary outcomes, including symptoms and left ventricular function, were also evaluated. RESULTS In 135 centers, 2789 patients with early atrial fibrillation (median time since diagnosis, 36 days) underwent randomization. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. A first-primary-outcome event occurred in 249 of the patients assigned to early rhythm control (3.9 per 100 person-years) and in 316 patients assigned to usual care (5.0 per 100 person-years) (hazard ratio, 0.79; 96% confidence interval, 0.66 to 0.94; P=0.005). The mean (±SD) number of nights spent in the hospital did not differ significantly between the groups (5.8±21.9 and 5.1±15.5 days per year, respectively; P=0.23). The percentage of patients with a primary safety outcome event did not differ significantly between the groups; serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% of the patients assigned to usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups. CONCLUSIONS Early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease