Identification of key biomarkers in Angelman syndrome by a multi-cohort analysis

Abstract

The Angelman Syndrome (AS) is an extreme neurodevelopmental disorder without effective treatments. While most patients with this disease can be diagnosed by genetic testing, there are still a handful of patients have an unrecognized genetic cause for their illness. Thus, novel approaches to clinical diagnosis and treatment are urgently needed. The aim of this study was to identify and characterize differentially expressed genes involved in AS and built potential diagnostic panel for AS by NGS sequencing. A multi-cohort analysis framework was used to analyze stem cell-derived neurons from AS patients in GSE160747 dataset. We identified three differentially expressed genes (ACTN1, ADAMTS2, SLC30A8) differentiates AS patients from controls. Moreover, we validated the expression patterns of these genes in GSE146640, GSE120225. Receiver operating characteristic (ROC) curves analysis demonstrated that these genes could function as potential diagnostic biomarkers [AUC = 1 (95% CI 1–1)]. This study may provide new approach for diagnosing patients with AS and helping to develop novel therapies in treating AS patients.

Trans-ancestry epigenome-wide association meta-analysis of DNA methylation with lifetime cannabis use

“…The genes annotated to these five cannabis use-associated CpGs are relevant to a range of health outcomes. [34][35][36][37][38][39][40][41][42][43][44] The five epigenome-wide significant CpGs are annotated to the nearest genes: LINC01132, ADGRF1, ADAM12, ACTN1, and APOBR. Of these, cg01101459-LINC01132, cg00813162-ACTN1, and cg14237301-APOBR were inversely associated with cannabis use, meaning that individuals who had used cannabis had lower DNAm at these CpG sites compared to those who had never used cannabis.…”

“…35 Genetic variants and differential expression of the ACTN1 have been reported in various diseases, including congenital macrothrombocytopenia, Angelman syndrome, Bowen disease, postmenopausal osteoporosis, lupus erythematosus, and COVID-19. [35][36][37][38]47,48 APOBR (Apolipoprotein B receptor) encodes a receptor protein that binds to dietary triglyceride-rich lipoproteins.…”