MicroRNA serum profiles and chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the last decade, the interest of micro RNAs (miRNAs) in the pathophysiological process of cGVHD has increased. The objectives of this study were to investigate a wide range of serum miRNAs in allografted patients and identify associations between miRNAs and cGVHD. The study included 79 allotransplanted adults, where serum samples were obtained 1 year after the allo-HSCT, and miRNA profiling analysis in serum was performed. Fifty of the 79 patients (63%) had signs of cGVHD at the 1-year post–allo-HSCT control. miRNA sequencing analysis revealed 1380 different miRNAs detected for at least 1 patient, whereas 233 miRNAs (17%) were detected in >70 patients. We identified 10 miRNAs that differed significantly between patients with and without cGVHD (P 75 of the patients. Furthermore, 5 distinct miRNAs, miR-365-3p, miR-148-3p, miR-122-5p, miR-378-3p, and miR-192-5p, were found to be particularly associated with cGVHD in our analysis and were validated by receiver operating characteristics analysis. Based on only 3 miRNAs, miR-365-3p, miR-148-3p, and miR-378-3p, we developed a miRNA signature that, by bioinformatic approaches and linear regression model, utterly improved our potential diagnostic biomarker model for cGVHD. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings.publishedVersio

Parental education and the risk of cerebral palsy for children:an evaluation of causality

Aim To explore whether increasing parental education has a causal effect on risk of cerebral palsy (CP) in the child, or whether unobserved confounding is a more likely explanation. Method We used data from Norwegian registries on approximately 1.5 million children born between 1967 and 2011. We compared results from a traditional cohort design with results from a family‐based matched case–control design, in which children with CP were matched to their first cousins without CP. In addition, we performed a simulation study to assess the role of unobserved confounding. Results In the cohort design, the odds of CP were reduced in children of mothers and fathers with higher education (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.60–0.75 for maternal education, and adjusted OR 0.75, 95% CI 0.67–0.85 for paternal education). In the family‐based case–control design, only an association for maternal education remained (adjusted OR 0.80, 95% CI 0.64–0.99). Results from a simulation study suggested that this association could be explained by unobserved confounding. Interpretation A causal effect of obtaining higher education on risk of CP in the child is unlikely. Results stress the importance of continued research on the role of genetic and environmental risk factors that vary by parents’ educational level.publishedVersio

Parental education and the risk of cerebral palsy for children: an evaluation of causality

Aim To explore whether increasing parental education has a causal effect on risk of cerebral palsy (CP) in the child, or whether unobserved confounding is a more likely explanation. Method We used data from Norwegian registries on approximately 1.5 million children born between 1967 and 2011. We compared results from a traditional cohort design with results from a family‐based matched case–control design, in which children with CP were matched to their first cousins without CP. In addition, we performed a simulation study to assess the role of unobserved confounding. Results In the cohort design, the odds of CP were reduced in children of mothers and fathers with higher education (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.60–0.75 for maternal education, and adjusted OR 0.75, 95% CI 0.67–0.85 for paternal education). In the family‐based case–control design, only an association for maternal education remained (adjusted OR 0.80, 95% CI 0.64–0.99). Results from a simulation study suggested that this association could be explained by unobserved confounding. Interpretation A causal effect of obtaining higher education on risk of CP in the child is unlikely. Results stress the importance of continued research on the role of genetic and environmental risk factors that vary by parents’ educational level

MicroRNA serum profiles and chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) is the most common long-term complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). During the last decade, the interest of micro RNAs (miRNAs) in the pathophysiological process of cGVHD has increased. The objectives of this study were to investigate a wide range of serum miRNAs in allografted patients and identify associations between miRNAs and cGVHD. The study included 79 allotransplanted adults, where serum samples were obtained 1 year after the allo-HSCT, and miRNA profiling analysis in serum was performed. Fifty of the 79 patients (63%) had signs of cGVHD at the 1-year post–allo-HSCT control. miRNA sequencing analysis revealed 1380 different miRNAs detected for at least 1 patient, whereas 233 miRNAs (17%) were detected in >70 patients. We identified 10 miRNAs that differed significantly between patients with and without cGVHD (P 75 of the patients. Furthermore, 5 distinct miRNAs, miR-365-3p, miR-148-3p, miR-122-5p, miR-378-3p, and miR-192-5p, were found to be particularly associated with cGVHD in our analysis and were validated by receiver operating characteristics analysis. Based on only 3 miRNAs, miR-365-3p, miR-148-3p, and miR-378-3p, we developed a miRNA signature that, by bioinformatic approaches and linear regression model, utterly improved our potential diagnostic biomarker model for cGVHD. We conclude that miRNAs are differently expressed among patients with and without cGVHD, although further and larger studies are needed to validate our present findings

Association between Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease: A Drug-wide Association Study

Background and Objectives The incidence rate of Parkinson disease (PD) has been increasing rapidly during the past years. Yet, no treatments exist to prevent or slow the progression of the disease. Moreover, we are unable to detect early disease stages during which intervention with disease-modifying therapies is most likely to succeed. The objective of this study was to perform an agnostic drug-wide association study estimating the association between the use of any of the drugs prescribed in Norway and the subsequent risk of PD. Methods This registry-based cohort study use data from the entire Norwegian population between 2004 and 2019 linked to the Norwegian Prescription Registry, with more than 600 million individual prescriptions. Drug classes were screened according to Anatomical Therapeutic Chemical codes at level 2, corresponding to therapeutic subgroups. We used Cox regression models to estimate hazard ratios (HRs) and 95% CIs for the associations between drug classes and PD risk. All p values were corrected for multiple testing using the false discovery rate. In addition, we conducted sensitivity analyses of exposure definition as well as time-lag and dose-response analyses. Results The study population comprised 3,223,672 individuals, 15,849 of whom developed PD during the follow-up. We identified 31 drug classes that were statistically significantly associated with PD risk in Norway during the follow-up. Drugs acting on the renin-angiotensin system (HR 0.92, 95% CI 0.89–0.95), corticosteroids for systemic use (0.88, 95% CI 0.84–0.93), and vaccines (0.89, 95% CI 0.82–0.96) were associated with a decreased risk of PD even up to 10 years before PD onset. Drug classes used to treat symptoms related to prodromal signs of PD, such as constipation, urological issues, and depression, were associated with an increased risk of subsequent diagnosis of PD with HRs of 1.6 (95% CI 1.49–1.73), 1.48 (1.42–1.53), and 1.94 (1.87–2.01), respectively. Discussion This drug-wide study identified 31 drug classes that were associated with the PD risk change. It reveals the links of renin-angiotensin system medications, vaccines, and corticosteroids with PD risk and suggests that monitoring drug usage using pharmacoepidemiology may allow identifying individuals with prodromal PD.publishedVersio