Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Cloudbasierte Infrastruktur für Bibliotheksdaten – auf dem Weg zu einer Neuordnung der deutschen Verbundlandschaft

Im Oktober 2012 hatte die Deutsche Forschungsgemeinschaft (DFG) ein Förderprogramm zur Neuausrichtung überregionaler Informationsservices ausgeschrieben, um eine umfassende Reorganisation bestehender Infrastrukturen anzustoßen, die mit den Empfehlungen des Wissenschaftsrates zur Zukunft der bibliothekarischen Verbundsysteme in Deutschland gefordert wurde. Im Themenfeld „Bibliotheksdateninfrastruktur und Lokale Systeme“ der DFG-Ausschreibung wurde das vom Hessischen Bibliotheksinformationssystem (HeBIS), vom Bibliotheksverbund Bayern (BVB) und vom Kooperativen Bibliotheksverbund Berlin-Brandenburg (KOBV) beantragte Vorhaben „Cloudbasierte Infrastruktur für Bibliotheksdaten“ (CIB) bewilligt. Das Projekt zielt auf die Überführung bibliothekarischer Workflows und Dienste in cloudbasierte Arbeitsumgebungen und die sukzessive Ablösung traditioneller Verbund- und Lokalsysteme durch internationale Systemplattformen. Zu den Arbeitspaketen des Vorhabens gehört u. a. die Einbindung von Norm- und Fremddatenangeboten und von weiteren Services in diese Plattformen.In October 2012 the Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) launched a funding programme for the reorganisation of the information services to encourage the redesign of existing infrastructures, which the Wissenschaftsrat (German Research Council) had called for in its recommendations for the future of library union catalogues in Germany. Under the issue of “Library data infrastructure and local systems” the library consortia of Hesse (HeBIS), Bavaria (BVB), and Berlin-Brandenburg (KOBV) applied successfully for the project “Cloud-based Infrastructure for Library Data” (CIB). The goals of the project aim at the transfer of library workflows and services to cloud environments. Traditional union catalogues and local systems will be replaced stepwise by international service platforms. The work packages of the project also include the integration of German authority data as well as further services into these platforms

Are th...

We operationalize scientific output in a region by means of the number of articles (as in the SciSearch database) per year and technology output by means of the number of patent applications (as in the database of the European Patent Office) per priority year. All informetric analyses were done using the DIALOG online-system. The main research questions are the following: Which scientific and technological fields or topics are most influent within a region and which institutions or companies are mainly publishing articles or holding patents? Do the distributions of regional science and technology fields and of publishing institutions follow the well-known informetric function? Are there – as it is expected – only few fields and few institutions which dominate th

Molecular Evolution of Early-Onset Prostate Cancer Identifies Molecular Risk Markers and Clinical Trajectories

Identifying the earliest somatic changes in prostate cancer can give important insights into tumor evolution and aids in stratifying high- from low-risk disease. We integrated whole genome, transcriptome and methylome analysis of early-onset prostate cancers (diagnosis ≤55 years). Characterization across 292 prostate cancer genomes revealed age-related genomic alterations and a clock-like enzymatic-driven mutational process contributing to the earliest mutations in prostate cancer patients. Our integrative analysis identified four molecular subgroups, including a particularly aggressive subgroup with recurrent duplications associated with increased expression of ESRP1, which we validate in 12,000 tissue microarray tumors. Finally, we combined the patterns of molecular co-occurrence and risk-based subgroup information to deconvolve the molecular and clinical trajectories of prostate cancer from single patient samples

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways