An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major ro
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PSYCHIATRY AND PRECLINICAL PSYCHIATRIC STUDIES - ORIGINAL 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 Ann‑Cathrine Berking1,2 · Christiane Thiel3 · Miriam A. Schiele3 · Christian Baumann1,4 · Raffael Kalisch5,6,7 · Swantje Notzen7,19 · Peter Zwanzger8,19,22 · Christiane A. Pané‑Farré9,14 · Alfons Hamm9 · Georg W. Alpers10 · Thomas Fydrich11 · Lydia Fehm11 · Alexander L. Gerlach12 · Benjamin Straube13 · Tilo Kircher13 · Winfried Rief14 · Jens Plag15 · Andreas Ströhle15 · Thomas Lang16,17 · Hans‑Ulrich Wittchen18,22 · Volker Arolt19 · Marcel Romanos20 · Paul Pauli4 · Andreas Reif21 · Jürgen Deckert1 · Katharina Domschke3,23 · Heike Weber1 Received: 10 March 2020 / Accepted: 8 May 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract 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. Keywords DNMT3A · DNMT3B · Anxiety disorders · Panic disorder · Generalized anxiety disorder · PSWQ · ASI · ACQ
Introduction Panic disorder (PD) with or without agoraphobia (AG) is among the most common mental disorders in the western countries with a lifetime prevalence ranging from 1 to 4% (Kessler et al. 2006; Somers et al. 2006). PD is characterized Electronic supplementary material The online version of this article (https://doi.org/10.1007/s0070
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