Journal Article

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes

Domschke, Katharina, Weber, Heike, Baumann, Christian, Schiele, Miriam A., Hamm, Alfons, Rief, Winfried, Reif, Andreas, Romanos, Marcel, Fehm, Lydia, Plag, Jens, Pané-Farré, Christiane A., Gerlach, Alexander L., Fydrich, Thomas, Lang, Thomas, Zwanzger, Peter, Ströhle, Andreas, Pauli, Paul, Berking, Ann-Cathrine, Notzen, Swantje, Alpers, Georg W., Arolt, Volker, Thiel, Christiane, Wittchen, Hans-Ulrich, Deckert, Jürgen, Kircher, Tilo, Straube, Benjamin, Kalisch, Raffael

2020

Overview

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation—DNA methyltransferases (DNMTs)—has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

• Publisher: Springer Vienna,Springer Nature B.V
• Subject: Age / Agoraphobia / Alleles / Anxiety disorders / Cognition / Dimensional analysis / DNA methylation / DNMT3B gene / Epigenetics / Funding / Genes / Genetic variability / Genotype & phenotype / Haplotypes / Medicine / Medicine & Public Health / Mental disorders / Neurology / Neurosciences / Panic attacks / Pathogenesis / Phenotypes / Polymorphism / Psychiatry / Psychiatry and Preclinical Psychiatric Studies - Original Article / Questionnaires / Single-nucleotide polymorphism / Statistical analysis / Statistical power / Suicides & suicide attempts