“DNA Methylation signatures in panic disorder”

Abstract

Panic disorder (PD) affects about four million Europeans, with women affected twice as likely as men, causing substantial suffering and high economic costs. The etiopathogenesis of PD remains largely unknown, but both genetic and environmental factors contribute to risk. An epigenome-wide association study (EWAS) was conducted to compare medication-free PD patients (n = 89) with healthy controls (n = 76) stratified by gender. Replication was sought in an independent sample (131 cases, 169 controls) and functional analyses were conducted in a third sample (N = 71). DNA methylation was assessed in whole blood using the Infinium HumanMethylation450 BeadChip. One genome-wide association surviving FDR of 5% (cg07308824, P = 1.094 × 10-7, P-adj = 0.046) was identified in female PD patients (N = 49) compared to controls (N = 48). The same locus, located in an enhancer region of the HECA gene, was also hypermethylated in female PD patients in the replication sample (P = 0.035) and the significance of the association improved in the meta-analysis (P-adj = 0.004). Methylation at this CpG site was associated with HECA mRNA expression in another independent female sample (N = 71) both at baseline (P = 0.046) and after induction by dexamethasone (P = 0.029). Of 15 candidates, 5 previously reported as associated with PD or anxiety traits also showed differences in DNA methylation after gene-wise correction and included SGK1, FHIT, ADCYAP1, HTR1A, HTR2A. Our study examines epigenome-wide differences in peripheral blood for PD patients. Our results point to possible sex-specific methylation changes in the HECA gene for PD but overall highlight that this disorder is not associated with extensive changes in DNA methylation in peripheral blood.

Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients

“…Furthermore, there were 9341 (2.99%) CpG probes with even lower maximum value than that of cg05293407 TRIM27 indicating its narrow range was reasonable. Meanwhile, plenty of studies have revealed that aberrant DNA methylations of these hypo-methylated CpG probes were also involved in diseases (e.g., female panic disorder risk associated cg07308824 HECA and paediatric medulloblastoma prognosis associated cg02257300 ERCC2 ) [48,49].…”

DNA methylation in adolescents with anxiety disorder: a longitudinal study

“…They depicted forty CpG sites significant associated with PD at 5% FDR correction, but with small different rates of the DNA methylation. A study that compared medication-free PD patients with healthy controls 25 suggested a possible sex-specific methylation process (hypermethylation in female patients) in the HECA gene, but no global changes in DNA methylation. Schartner et al .…”

“…Given the current state of knowledge on the genetics of anxiety disorders, unbiased hypothesis-free methodology might be more fruitful for investigating the DNA methylation fingerprints related to the course of these disorders 19 – 21 . To our knowledge there is a paucity of studies involving genome-wide DNA methylation and anxiety in humans 22 – 25 and in animals 26 studies.…”

Genetic and epigenetic analyses of panic disorder in the post-GWAS era

“…EWAS can be used to analyze genome-wide associations between epigenetic changes and disorders, and several EWAS for multifactorial disorders, including mental disorders, have been reported (Abdulrahim et al 2019;Starnawska et al 2019;Gonzalez-Jaramillo et al 2019). Iurato et al (2017) conducted an EWAS in a sample of 89 patients with PD and 76 controls. In the female sample, one locus with genome-wide association was detected in the enhancer region of the hdc homolog, cell cycle regulator (HECA) gene (cg07308824: p = 1.094 × 10 −7 ; p-adj = 0.046).…”