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

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.

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References

  1. Alpers GW, Pauli P (2001) Angst-Sensitivitäts-Index (ASI). Julius-Maximilians-Universität Würzburg, Würzburg

    Google Scholar 

  2. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®), 5th edn. American Psychiatric Association, Washington

    Book  Google Scholar 

  3. Bandelow B, Baldwin D, Abelli M, Altamura C, Dell'Osso B, Domschke K, Fineberg NA, Grunblatt E, Jarema M, Maron E, Nutt D, Pini S, Vaghi MM, Wichniak A, Zai G, Riederer P (2016) Biological markers for anxiety disorders, OCD and PTSD—a consensus statement Part I: Neuroimaging and genetics. World J Biol Psychiatry 17:321–365

    Article  Google Scholar 

  4. Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics (Oxford, England) 21:263–265

    CAS  Article  Google Scholar 

  5. Baumann C, Klauke B, Weber H, Domschke K, Zwanzger P, Pauli P, Deckert J, Reif A (2013) The interaction of early life experiences with COMT val158met affects anxiety sensitivity. Genes Brain Beh 12:821–829

    CAS  Article  Google Scholar 

  6. Broad Institute of MIT and Harvard (2006) Haploview. https://www.broadinstitute.org/haploview/haploview. Accessed 10 Jan 2020

  7. Cosci F, Knuts IJ, Abrams K, Griez EJ, Schruers KR (2010) Cigarette smoking and panic: a critical review of the literature. J Clin Psychiatry 71:606–615

    Article  Google Scholar 

  8. Craske MG, Stein MB, Eley TC, Milad MR, Holmes A, Rapee RM, Wittchen HU (2017) Anxiety disorders. Nat Rev Dis Prim 3:17024

    Article  Google Scholar 

  9. de Jonge P, Roest AM, Lim CC, Florescu SE, Bromet EJ, Stein DJ, Harris M, Nakov V, Caldas-de-Almeida JM, Levinson D, Al-Hamzawi AO, Haro JM, Viana MC, Borges G, O'Neill S, de Girolamo G, Demyttenaere K, Gureje O, Iwata N, Lee S, Hu C, Karam A, Moskalewicz J, Kovess-Masfety V, Navarro-Mateu F, Browne MO, Piazza M, Posada-Villa J, Torres Y, Ten Have ML, Kessler RC, Scott KM (2016) Cross-national epidemiology of panic disorder and panic attacks in the world mental health surveys. Depress Anxiety 33:1155–1177

    Article  Google Scholar 

  10. Domschke K, Reif A, Weber H, Richter J, Hohoff C, Ohrmann P, Pedersen A, Bauer J, Suslow T, Kugel H, Heindel W, Baumann C, Klauke B, Jacob C, Maier W, Fritze J, Bandelow B, Krakowitzky P, Rothermundt M, Erhardt A, Binder EB, Holsboer F, Gerlach AL, Kircher T, Lang T, Alpers GW, Strohle A, Fehm L, Gloster AT, Wittchen HU, Arolt V, Pauli P, Hamm A, Deckert J (2011) Neuropeptide S receptor gene—converging evidence for a role in panic disorder. Mol Psychiatry 16:938–948

    CAS  Article  Google Scholar 

  11. Domschke K, Tidow N, Schrempf M, Schwarte K, Klauke B, Reif A, Kersting A, Arolt V, Zwanzger P, Deckert J (2013) Epigenetic signature of panic disorder: a role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation? Prog Neuropsychopharmacol Biol Psychiatry 46:189–196

    CAS  Article  Google Scholar 

  12. Ehlers A, Margraf J, Chambless DL (1993) Fragebogen zu körperbezogenen Ängsten. Kognitionen und Vermeidung. AKV Beltz Test, Weinheim

    Google Scholar 

  13. Elliott E, Manashirov S, Zwang R, Gil S, Tsoory M, Shemesh Y, Chen A (2016) Dnmt3a in the medial prefrontal cortex regulates anxiety-like behavior in adult mice. J Neurosci 36:730–740

    CAS  Article  Google Scholar 

  14. Faul F, Erdfelder E, Buchner A, Lang AG (2009) Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 41:1149–1160

    Article  Google Scholar 

  15. Feng J, Zhou Y, Campbell SL, Le T, Li E, Sweatt JD, Silva AJ, Fan G (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13:423–430

    CAS  Article  Google Scholar 

  16. Genetics and Bioinformatics Team-Aix Marseille Université (2017) Human Splicing Finder. https://umd.be/HSF3/. Accessed 21 Dec 2017

  17. He C, Holme J, Anthony J (2014) SNP genotyping: the KASP assay. Methods Mol Biol (Clifton, NJ) 1145:75–86

    CAS  Article  Google Scholar 

  18. Hettema JM, Neale MC, Kendler KS (2001) A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 158:1568–1578

    CAS  Article  Google Scholar 

  19. Holt RI, Phillips DI, Jameson KA, Cooper C, Dennison EM, Peveler RC (2013) The relationship between depression, anxiety and cardiovascular disease: findings from the Hertfordshire Cohort Study. J Affect Dis 150:84–90

    Article  Google Scholar 

  20. Howe AS, Buttenschon HN, Bani-Fatemi A, Maron E, Otowa T, Erhardt A, Binder EB, Gregersen NO, Mors O, Woldbye DP, Domschke K, Reif A, Shlik J, Koks S, Kawamura Y, Miyashita A, Kuwano R, Tokunaga K, Tanii H, Smoller JW, Sasaki T, Koszycki D, De Luca V (2016) Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways. Mol Psychiatry 21:665–679

    CAS  Article  Google Scholar 

  21. Kessler RC, Chiu WT, Jin R, Ruscio AM, Shear K, Walters EE (2006) The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Arch General Psychiatry 63:415–424

    Article  Google Scholar 

  22. Kessler RC, Alonso J, Chatterji S, He Y (2014) Disability and costs the wiley handbook of anxiety disorders. John Wiley & Sons, Ltd., Chichester

    Google Scholar 

  23. Kyrou I, Kollia N, Panagiotakos D, Georgousopoulou E, Chrysohoou C, Tsigos C, Randeva HS, Yannakoulia M, Stefanadis C, Papageorgiou C, Pitsavos C (2017) Association of depression and anxiety status with 10-year cardiovascular disease incidence among apparently healthy Greek adults: The ATTICA Study. Eur J Prev Cardiol 24:145–152

    Article  Google Scholar 

  24. LaPlant Q, Vialou V, Covington HE 3rd, Dumitriu D, Feng J, Warren BL, Maze I, Dietz DM, Watts EL, Iniguez SD, Koo JW, Mouzon E, Renthal W, Hollis F, Wang H, Noonan MA, Ren Y, Eisch AJ, Bolanos CA, Kabbaj M, Xiao G, Neve RL, Hurd YL, Oosting RS, Fan G, Morrison JH, Nestler EJ (2010) Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens. Nat Neurosci 13:1137–1143

    CAS  Article  Google Scholar 

  25. LGC Limeted (2013) KASP genotyping chemistry. User guide and manual. https://www.lgcgroup.com/LGCGroup/media/PDFs/Products/Genotyping/KASP-genotyping-chemistry-User-guide.pdf. Accessed 19 Nov 2017

  26. LGC Limeted (2014) KASP genotyping. Quick start guide. Accessed 21 Nov 2017

  27. Lin PI, Vance JM, Pericak-Vance MA, Martin ER (2007) No gene is an island: the flip-flop phenomenon. Am J Hum Genet 80:531–538

    CAS  Article  Google Scholar 

  28. Miller CA, Sweatt JD (2007) Covalent modification of DNA regulates memory formation. Neuron 53:857–869

    CAS  Article  Google Scholar 

  29. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16:1215

    CAS  Article  Google Scholar 

  30. Murphy TM, Mullins N, Ryan M, Foster T, Kelly C, McClelland R, O'Grady J, Corcoran E, Brady J, Reilly M, Jeffers A, Brown K, Maher A, Bannan N, Casement A, Lynch D, Bolger S, Buckley A, Quinlivan L, Daly L, Kelleher C, Malone KM (2013) Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients. Genes Brain Behav 12:125–132

    CAS  Article  Google Scholar 

  31. National Center for Biotechnology Information (2017a) Reference SNP (refSNP) Cluster Report: rs1465764. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1465764. Accessed 13 Dec 2017

  32. National Center for Biotechnology Information (2017b) Reference SNP (refSNP) Cluster Report: rs1465825. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=1465825. Accessed 13 Dec 2017

  33. National Center for Biotechnology Information (2017c) Reference SNP (refSNP) Cluster Report: rs2424932 U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=2424932. Accessed 13 Dec 2017

  34. National Center for Biotechnology Information (2017d) Reference SNP (refSNP) Cluster Report: rs4911259 U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=4911259. Accessed 13 Dec 2017

  35. National Center for Biotechnology Information (2017e) Reference SNP (refSNP) Cluster Report: rs11683424 U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=11683424. Accessed 13 Dec 2017

  36. National Institute of Environmental Health Sciences (2017) SNP Function Prediction (FuncPred). https://manticore.niehs.nih.gov/snpinfo/snpfunc.html. Accessed 21 Dec 2017

  37. Otowa T, Hek K, Lee M, Byrne EM, Mirza SS, Nivard MG, Bigdeli T, Aggen SH, Adkins D, Wolen A, Fanous A, Keller MC, Castelao E, Kutalik Z, der Auwera SV, Homuth G, Nauck M, Teumer A, Milaneschi Y, Hottenga JJ, Direk N, Hofman A, Uitterlinden A, Mulder CL, Henders AK, Medland SE, Gordon S, Heath AC, Madden PA, Pergadia ML, van der Most PJ, Nolte IM, van Oort FV, Hartman CA, Oldehinkel AJ, Preisig M, Grabe HJ, Middeldorp CM, Penninx BW, Boomsma D, Martin NG, Montgomery G, Maher BS, van den Oord EJ, Wray NR, Tiemeier H, Hettema JM (2016) Meta-analysis of genome-wide association studies of anxiety disorders. Mol Psychiatry 21:1485

    CAS  Article  Google Scholar 

  38. Pishva E, Drukker M, Viechtbauer W, Decoster J, Collip D, van Winkel R, Wichers M, Jacobs N, Thiery E, Derom C, Geschwind N, van den Hove D, Lataster T, Myin-Germeys I, van Os J, Rutten BP, Kenis G (2014) Epigenetic genes and emotional reactivity to daily life events: a multi-step gene-environment interaction study. PLoS ONE 9:e100935

    Article  Google Scholar 

  39. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559–575

    CAS  Article  Google Scholar 

  40. R Core Team (2014) R: A language and environment for statistical computing. R Foundation for Statistical Computing. https://www.R-project.org/.

  41. Sapsford KE, Berti L, Medintz IL (2006) Materials for fluorescence resonance energy transfer analysis: beyond traditional donor-acceptor combinations. Angew Chem Int Ed Engl 45:4562–4589

    CAS  Article  Google Scholar 

  42. Schiele MA, Ziegler C, Holitschke K, Schartner C, Schmidt B, Weber H, Reif A, Romanos M, Pauli P, Zwanzger P, Deckert J, Domschke K (2016) Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study. J Neural Transm (Vienna Austria: 1996) 123:895–904

    CAS  Article  Google Scholar 

  43. Sipahi L, Wildman DE, Aiello AE, Koenen KC, Galea S, Abbas A, Uddin M (2014) Longitudinal epigenetic variation of DNA methyltransferase genes is associated with vulnerability to post-traumatic stress disorder. Psychol Med 44:3165–3179

    CAS  Article  Google Scholar 

  44. Somers JM, Goldner EM, Waraich P, Hsu L (2006) Prevalence and incidence studies of anxiety disorders: a systematic review of the literature. Can J Psychiatry Revue canadienne de psychiatrie 51:100–113

    Article  Google Scholar 

  45. Stöber J (1995) Besorgnis: Ein Vergleich dreier Inventare zur Erfassung allgemeiner Sorgen. Zeitschrift für Differentielle und Diagnostische Psychologie 16(50):63

    Google Scholar 

  46. World Health Organisation (1992) The ICD-10 classification of mental and behavioural disorders : clinical descriptions and diagnostic guidelines; ICD-10/World Health Organization Geneva. WHO, Geneva

    Google Scholar 

  47. Ziegler C, Richter J, Mahr M, Gajewska A, Schiele MA, Gehrmann A, Schmidt B, Lesch KP, Lang T, Helbig-Lang S, Pauli P, Kircher T, Reif A, Rief W, Vossbeck-Elsebusch AN, Arolt V, Wittchen HU, Hamm AO, Deckert J, Domschke K (2016) MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy. Transl Psychiatry 6:e773

    CAS  Article  Google Scholar 

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Acknowledgements

We are grateful to all individuals who participated in this study either as part of the CRC-TRR-58 Mega Study wave 1 and 2 or the German PanicNet wave 1 [multicenter trial “Mechanisms of Action in CBT (MAC)”] or wave 2 [multicenter trial “Mechanisms of CBT-treatment effects in patients with panic disorder and panic disorder with agoraphobia: The role of interoceptive exposure and fear augmentation (MCBT-PDAS)”] studies. This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—project number 44541416—TRR 58 “Fear, Anxiety, Anxiety Disorders”, project Z02 to JD, AR, MR and PP, B01 to PP, B06 to AR, B07 to TL, and C02 to KD and JD. RK was supported by the DFG grant KA1623/3-1. The MAC study was funded by the German Federal Ministry of Education and Research (BMBF; project no. 01GV0615) as part of the BMBF Psychotherapy Research Funding Initiative. The principal investigators (PIs) of the centers with respective areas of responsibility in the MAC study are: V. Arolt (Münster: Overall MAC Program Coordination), H.-U. Wittchen (Dresden: PI for the Randomized Clinical Trial and Manual Development), A. Hamm (Greifswald: PI for Psychophysiology), A. L. Gerlach (Münster: PI for Psychophysiology and Panic subtypes), A. Ströhle (Berlin: PI for Experimental Pharmacology), T. Kircher (Marburg: PI for functional neuroimaging) and J. Deckert (Würzburg: PI for Genetics). Additional site directors in the randomized controlled trial component of the program are as follows: G. W. Alpers (Würzburg), T. Fydrich and L. Fehm (Berlin-Adlershof) and T. Lang (Bremen). Acknowledgements and staff members by site: Greifswald (coordinating site for Psychophysiology): Christiane Pané-Farré, Jan Richter, Susan Richter, Matthias von Rad; Berlin-Charité (coordinating Center for Experimental Pharmacology): Harald Bruhn, Anja Siegmund, Meline Stoy, André Wittmann; Berlin-Adlershof: Irene Schulz; Münster (Overall MAC Program Coordination, Genetics and Functional Neuroimaging): Andreas Behnken, Katharina Domschke, Adrianna Ewert, Carsten Konrad, Bettina Pfleiderer, Christina Uhlmann, Peter Zwanzger; Münster (coordinating site for psychophysiology and subtyping): Judith Eidecker, Swantje Koller, Fred Rist, Anna Vossbeck-Elsebusch; Marburg/Aachen (coordinating center for functional neuroimaging): Barbara Drüke, Sonja Eskens, Thomas Forkmann, Siegfried Gauggel, Susan Gruber, Andreas Jansen, Thilo Kellermann, Isabelle Reinhardt, Nina Vercamer-Fabri; Dresden (coordinating site for data collection, analysis, and the RCT): Franziska Einsle, Christine Froehlich, Andrew T. Gloster, Christina Hauke, Simone Heinze, Michael Hoefler, Ulrike Lueken, Peter Neudeck, Stephanie Preiß, Dorte Westphal; Würzburg Psychiatry Department (coordinating center for genetics): Andreas Reif, Caro Gagel; Würzburg Psychology Department: Julia Duerner, Hedwig Eisenbarth, Antje B. M. Gerdes, Harald Krebs, Paul Pauli, Silvia Schad, Nina Steinhäuser; Bremen: Veronika Bamann, Sylvia Helbig-Lang, Anne Kordt, Pia Ley, Franz Petermann, Eva-Maria Schroeder. Additional support was provided by the coordinating center for clinical studies in Dresden (KKS Dresden): Xina Graehlert and Marko Käppler. The MCBT-PDAS study was funded by the German Federal Ministry of Education and Research (BMBF, 01GV0614) as part of the larger BMBF Psychotherapy Research Funding Initiative Improving the Treatment of Panic Disorder. Principal investigators (PI) with respective areas of competence of the MCBT-PDAS are Alfons Hamm (Greifswald: PI Psychophysiology); Thomas Lang (Bremen: Study Director for the Randomized Clinical Trial (RCT) and Manual Development); Alexander L. Gerlach (Münster: PI Panic subtypes); Georg W. Alpers (Mannheim: PI Ambulatory assessment); Christiane Pané-Farré (Greifswald: PI Psychophysiology and Panic Disorder); Tilo Kircher (Marburg: PI for functional neuroimaging), and Jürgen Deckert (Würzburg: PI for Genetics). Additional site directors in the RCT component of the program are Winfried Rief (Marburg), and Paul Pauli (Würzburg). Centers of the Research Network: Volker Arolt (Münster: Overall Network Coordination), Hans-Ulrich Wittchen (Dresden), Andreas Ströhle (Berlin). Data Access and Responsibility: All principle investigators take responsibility for the integrity of the respective study data and their components. All authors and co-authors had full access to all study data. Data analysis and manuscript preparation were completed by the authors and co-authors of this article, who take responsibility for its accuracy and content. Acknowledgements and staff members by site: Bremen (coordinating center for the multicenter trial): Veronika Bamann, Sandra Cammin, Sarah Czilwik, Kira Geisler, Sylvia Helbig-Lang, Kirsten Helmes, Anne Kordt, Tanja Leonhard, Mila Plett-Perelshteyn, Christian Soltau, Juliane Sülz, Maxie von Auer; Greifswald (coordinating site for psychophysiology): Anett Hoffmann, Jan Richter; Mannheim (coordinating center for ambulatory assessment): Christoph Biwer, Elisabeth Borgmann, Antje Gerdes, Otto Martin, Kristina Steinbach, Bettina Stemmler, Andrew White; Marburg (coordinating center for functional neuroimaging): Tobias Fehlinger, Andreas Jansen, Nikita Jegan, Carsten Konrad, Marion Mickeler, Silke Rusch, Katrin Schlötterer, Benjamin Straube, Mareike Stumpenhorst, Katrin Wambach, Yunbo Yang; Münster (coordinating site for panic subtypes): Susanne Kettler, Anna Vossbeck-Elsebusch; Würzburg Psychiatry Department (coordinating center for genetics): Carola Gagel, Andreas Reif, Heike Weber; Würzburg Psychology Department: Almut Friedl-Huber, Harald Krebs, Caroline Ott, Nina Steinhäuser; Additional support was provided by the coordinating center for clinical studies in Dresden (KKS Dresden): Marko Käppler. The study was registered with the NCT01323556. T. Lonsdorf and D. Schümann are credited for CRC-TRR-58 Mega Study wave 1 and 2 recruitement at Hamburg and C. Gagel, N. Döring and I. Reck for excellent technical assistance at Würzburg.

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Over the last years, V. Arolt has been a member of the advisory boards and/or gave presentations for the following companies: Astra-Zeneca, Eli Lilly, Janssen-Organon, Lundbeck, Otsuka, Servier, and Trommsdorff. He also received sponsorships for symposia and educational activities from Astra-Zeneca, Jansen-Organon, Lundbeck and Servier. K. Domschke is a member of the Janssen Pharmaceuticals, Inc. Steering Committee Neurosciences. R. Kalisch receives advisory honoraria from JoyVentures, Herzlia, Israel. T. Kircher received fees for educational programs from Janssen, Eli Lilly, Servier, Lundbeck, Bristol Myers Squibb, Pfizer and Astra-Zeneca. P. Pauli is a shareholder of a commercial company that develops virtual environment research systems for empirical studies in the field of psychology, psychiatry, and psychotherapy. A. Ströhle received research funding from Lundbeck, and speaker honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly & Co, Lundbeck, Pfizer, Wyeth and UCB. He was a consultant for Actelion. Educational grants were given by the Boehringer Ingelheim Fonds, the Eli Lilly International Foundation, Janssen-Cilag, Pfizer and Eli Lilly & Co. H.-U. Wittchen has served as a general consultant (non-product related) for Pfizer, Lundbeck, Organon, Servier and EssexPharma and has received grant funding for his institution from Sanofi Aventis, Pfizer, Lundbeck, Novatis, Essex Pharma, Servier and Wyeth. These cooperations have no relevance to the work that is covered in the manuscript. The other authors declare no conflict of interest.

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Berking, AC., Thiel, C., Schiele, M.A. et al. 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. J Neural Transm 127, 1527–1537 (2020). https://doi.org/10.1007/s00702-020-02206-x

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Keywords

  • DNMT3A
  • DNMT3B
  • Anxiety disorders
  • Panic disorder
  • Generalized anxiety disorder
  • PSWQ
  • ASI
  • ACQ