Multi-Omics of the Iron Homeostasis Pathway in Patient Outcomes after Aneurysmal Subarachnoid Hemorrhage

Patient outcomes after aneurysmal subarachnoid hemorrhage (aSAH) are variable and healthcare providers are often unable to predict those who will do poorly and are in need of more intensive nursing management. This ancillary, longitudinal, observational, candidate gene association study investigated the hypothesis that epigenetic and genetic variability of genes in the iron homeostasis pathway may account for a proportion of variability in patient outcomes post-aSAH. This study was conducted using a two-tier design (targeted discovery and replication) and capitalized on an existing cohort of aSAH participants with genome-wide DNA methylation, genotype, and patient outcome data as well as stored biosamples. This study used group-based trajectory analysis (Aim 1), binary logistic regression (Aims 1 and 2), and Bayesian statistical methods (Aim 2) to assess the relationship between inferred DNA methylation trajectory groups (Aim 1) and tagging SNPs (Aim 2) from iron homeostasis candidate genes (n = 39) and acute (cerebral vasospasm [CV] and delayed cerebral ischemia [DCI]) and long-term (Glasgow Outcome Scale [GOS] and death at 3 and 12-months) patient outcomes post-aSAH. In Aim 1, we identified three DNA methylation sites in three candidate genes (Amyloid Precursor Protein [APP], STEAP3 metalloreductase [STEAP3], and Tumor Necrosis Factor [TNF]) with inferred trajectory groups significantly associated with patient outcomes in our discovery sample. Specifically, associations were identified between cg08866780 (APP) and GOS at 12 months (p = 0.0001) and death at 3 and 12 months (both p=0.0002); cg25713625 (STEAP3) and GOS at 3 and 12 months (p = 0.00005 and p = 0.0005, respectively) and death at 3 and 12 months (p = 0.0013 and p = 0.0015, respectively); and cg08553327 (TNF) with GOS at 3 months (p = 0.00001). Replication data are pending. For Aim 2, we identified two SNPs in two candidate genes (Ceruloplasmin [CP] and Cubilin [CUBN]) that were associated with patient outcomes in both the discovery and replication samples. Specifically, rs10904850 (CUBN) was significantly associated with DCI (mega-analysis combining targeted discovery and replication samples, p = 0.004) and rs17838831 (CP) with GOS at 3 and 12 months (mega-analysis p = 0.0004 and p = 0.057, respectively)

Exercitium Juridicum Primum Propositis Ex Jure Publico Imperii Romano-Germanici : Uti Et è Disciplina Diplomatica Thesibus, Quod Adsensu Venerandae Facultatis Juridicae

Subibit ... D. Goswinus ab Heinsberg, Agrippinas, Opponentibus D. Joanne Georgio Maass, D. Joanne Josepho Gade Agrippinatibus. In Auditorio Majori Juridico Die [] Januarii. An. MDCCLXXXVIIAutopsie nach Ex. der ULB DüsseldorfVorlageform der Veröffentlichungsangabe: Coloniae, Ex Typographia VniversitatisTagesangabe fehlt im Druc

BISON-Integration 'Betrieb' und 'Fahrzeuginstandhaltung' bei der Kreiswerke Heinsberg GmbH in Geilenkirchen Schlussbericht

Available from TIB Hannover: F93B958+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Mikrosensor SENTEX. Teilvorhaben 2: Beugungsoptischer Kanal Abschlussbericht

SIGLEAvailable from TIB Hannover: DtF QN1(113,43) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman

Schnellanalytik fuer Bauabfaelle - ein wichtiger Beitrag zur Kreislaufwirtschaft in der Baubranche Abschlussbericht

Available from TIB Hannover: F01B556 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDeutsche Bundesstiftung Umwelt, Osnabrueck (Germany)DEGerman

Generierung und Umsetzung des Heinsberger Informations- und Leitsystems unter Beruecksichtigung relevanter Bausteine aus BISON und BFB Schlussbericht

SIGLEAvailable from TIB Hannover: F95B1382+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

An exploratory study of white blood cell proportions across preeclamptic and normotensive pregnancy by self-identified race in individuals with overweight or obesity

Objective: Examine white blood cell (WBC) proportions across preeclamptic (n = 28 cases) and normotensive (n = 28 controls) pregnancy in individuals with overweight/obesity. Methods: WBC proportions were inferred from genome-wide DNA methylation data and compared by case/control status and self-identified race. Results: In Trimester 1, ean B cell proportions were suggestively lower in cases in the overall sample and significantly lower in White participants but not in Black participants. More significant WBC proportion changes were observed across normotensive than preeclamptic pregnancy. Conclusions: These findings in a small sample demonstrate need for additional studies investigating the relationship between self-identified race and WBCs in pregnancy