Epigenome-wide association study of DNA methylation in panic disorder. 2017

Mihoko Shimada-Sugimoto, and Takeshi Otowa, and Taku Miyagawa, and Tadashi Umekage, and Yoshiya Kawamura, and Miki Bundo, and Kazuya Iwamoto, and Mamoru Tochigi, and Kiyoto Kasai, and Hisanobu Kaiya, and Hisashi Tanii, and Yuji Okazaki, and Katsushi Tokunaga, and Tsukasa Sasaki
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo Ward, Tokyo, 113-0033 Japan.

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. β values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, β 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.

UI MeSH Term Description Entries
D008297 Male Males
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015894 Genome, Human The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs. Human Genome,Genomes, Human,Human Genomes
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D016131 Lymphocyte Subsets A classification of lymphocytes based on structurally or functionally different populations of cells. Lymphocyte Subpopulations,Lymphocyte Subpopulation,Lymphocyte Subset,Subpopulation, Lymphocyte,Subpopulations, Lymphocyte,Subset, Lymphocyte,Subsets, Lymphocyte
D016584 Panic Disorder A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. Panic Attacks,Attack, Panic,Attacks, Panic,Disorder, Panic,Disorders, Panic,Panic Attack,Panic Disorders
D044127 Epigenesis, Genetic A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression. Epigenetic Processes,Epigenetic Process,Epigenetics Processes,Genetic Epigenesis,Process, Epigenetic,Processes, Epigenetic,Processes, Epigenetics
D053263 Gene Regulatory Networks Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations. Gene Circuits,Gene Modules,Gene Networks,Transcriptional Networks,Gene Module,Circuit, Gene,Circuits, Gene,Gene Circuit,Gene Network,Gene Regulatory Network,Module, Gene,Modules, Gene,Network, Gene,Network, Gene Regulatory,Network, Transcriptional,Networks, Gene,Networks, Gene Regulatory,Networks, Transcriptional,Regulatory Network, Gene,Regulatory Networks, Gene,Transcriptional Network
D055106 Genome-Wide Association Study An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers to identify gene candidates or quantitative trait loci associated with a specific organism trait or specific disease or condition. Genome Wide Association Analysis,Genome Wide Association Study,GWA Study,Genome Wide Association Scan,Genome Wide Association Studies,Whole Genome Association Analysis,Whole Genome Association Study,Association Studies, Genome-Wide,Association Study, Genome-Wide,GWA Studies,Genome-Wide Association Studies,Studies, GWA,Studies, Genome-Wide Association,Study, GWA,Study, Genome-Wide Association

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