Epigenome-wide DNA methylation analysis of whole blood cells derived from patients with GAD and OCD in the Chinese Han population

Abstract

Generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) had high comorbidity and affected more than 44 million people around the world leading to a huge burden on health and economy. Here, we conducted an epigenome-wide DNA methylation study employing 93 patients with GAD, 65 patients with OCD, and 302 health controls, to explore epigenetic alterations associated with the onset and differences of GAD and OCD. We identified multiple differentially methylated positions (DMPs) and regions (DMRs): three DMP genes included RIOK3 (cg21515243, p = 8.00 × 10−10), DNASE2 (cg09379601, p = 1.10 × 10−9), and PSMB4 (cg01334186, p = 3.70 × 10−7) and two DMR genes USP6NL (p = 4.50 × 10−4) and CPLX1 (p = 6.95 × 10−4) were associated with the onset of GAD and OCD; three DMPs genes included LDLRAP1 (cg21400344, p = 4.40 × 10−12), ACIN1 (cg23712970, p = 2.98×10−11), and SCRT1 (cg25472897, p = 5.60 × 10−11) and three DMR genes WDR19 (p = 3.39 × 10−3), SYCP1 (p = 6.41 × 10−3), and FAM172A (p = 5.74 × 10−3) were associated with the differences between GAD and OCD. Investigation of epigenetic age and chronological age revealed a different epigenetic development trajectory of GAD and OCD. Conclusively, our findings which yielded robust models may aid in distinguishing patients from healthy controls (AUC = 0.90–0.99) or classifying patients with GAD and OCD (AUC = 0.89–0.99), and may power the precision medicine for them.

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response

“…In supporting our findings, three of our twelve most significant DMPs were found in a recent study comparing people with GAD, or OCD, with healthy controls of Chinese Han origin 49 . These probes map to RABGGTB, MPK8IP3, and ENAH genes.…”

“…Of the 305 probes identified by our analysis, 241 were annotated to 233 genes based on the Illumina annotation. Gene Ontology (GO) analysis, using the R package missMethyl (49,50), for the same probes did not show any term enriched after multiple test corrections. Of note, five terms from the GO analysis showed a nominal p-value < 0.05 (Supplementary table 5).…”

Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response

“…In supporting our findings, three of our twelve most significant DMPs were found in a recent study comparing people with generalized anxiety disorder (GAD), or OCD, with healthy controls of Chinese Han origin [ 80 ]. These probes map to RABGGTB , MPK8IP3 , and ENAH genes.…”

Bioinformatics gene analysis for potential biomarkers and therapeutic targets of Parkinson’s disease based on neutrophil extracellular traps

“…Xia et al found that epigenome-wide DNA methylation analysis of whole blood cells showed differential expression of CRT1 among individuals with generalized anxiety disorder (GAD), obsessivecompulsive disorder (OCD), and healthy controls. This suggests that CRT1 may help distinguishing patients from healthy controls or classifying patients with GAD and OCD (Guo et al, 2022). SCRT1 also regulated the conversion from microglia to neurons, which was crucial for nerve system development (Malygina et al, 2021).…”