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Altered immune phenotype and DNA methylation in panic disorder.

ABSTRACT: BACKGROUND:Multiple studies have related psychiatric disorders and immune alterations. Panic disorder (PD) has been linked with changes in leukocytes distributions in several small studies using different methods for immune characterization. Additionally, alterations in the methylation of repetitive DNA elements, such as LINE-1, have been associated with mental disorders. Here, we use peripheral blood DNA methylation data from two studies and an updated DNA methylation deconvolution library to investigate the relation of leukocyte proportions and methylation status of repetitive elements in 133 patients with panic disorder compared with 118 controls. METHODS AND RESULTS:We used DNA methylation data to deconvolute leukocyte cell-type proportions and to infer LINE-1 element methylation comparing PD cases and controls. We also identified differentially methylated CpGs associated with PD using an epigenome-wide association study approach (EWAS), with models adjusting for sex, age, and cell-type proportions. Individuals with PD had a lower proportion of CD8T cells (OR: 0.86, 95% CI: 0.78-0.96, P-adj?=?0.030) when adjusting for age, sex, and study compared with controls. Also, PD cases had significantly lower LINE-1 repetitive element methylation than controls (P?

SUBMITTER: Petersen CL

PROVIDER: S-EPMC7672933 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Project description:Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD.The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N?=?48, control, N?=?48) extracted from peripheral blood. Methylation arrays were used for the analysis. ? values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, ? values were converted to M values via the logit transformation for epigenome-wide association study. The relationship between each DNA methylation site and PD was assessed by linear regression analysis with adjustments for the effects of leukocyte subsets.Forty CpG sites showed significant association with PD at 5% FDR correction, though the differences of the DNA methylation levels were relatively small. Most of the significant CpG sites (37/40 CpG sites) were located in or around CpG islands. Many of the significant CpG sites (27/40 CpG sites) were located upstream of genes, and all such CpG sites with the exception of two were hypomethylated in PD subjects. A pathway analysis on the genes annotated to the significant CpG sites identified several pathways, including "positive regulation of lymphocyte activation."Although future studies with larger number of samples are necessary to confirm the small DNA methylation abnormalities associated with PD, there is a possibility that several CpG sites might be associated, together as a group, with PD.

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Altered immune phenotype and DNA methylation in panic disorder.

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