Forstner, Andreas J., Awasthi, Swapnil ORCID: 0000-0002-9692-8123, Wolf, Christiane, Maron, Eduard, Erhardt, Angelika, Czamara, Darina, Eriksson, Elias, Lavebratt, Catharina ORCID: 0000-0003-4987-2718, Allgulander, Christer, Friedrich, Nina, Becker, Jessica, Hecker, Julian, Rambau, Stefanie, Conrad, Rupert ORCID: 0000-0003-3207-2677, Geiser, Franziska ORCID: 0000-0002-4212-9692, McMahon, Francis J., Moebus, Susanne, Hess, Timo, Buerfent, Benedikt C., Hoffmann, Per, Herms, Stefan, Heilmann-Heimbach, Stefanie, Kockum, Ingrid ORCID: 0000-0002-0867-4726, Olsson, Tomas ORCID: 0000-0002-2938-1877, Alfredsson, Lars, Weber, Heike, Alpers, Georg W. ORCID: 0000-0001-9896-5158, Arolt, Volker, Fehm, Lydia, Fydrich, Thomas, Gerlach, Alexander L., Hamm, Alfons, Kircher, Tilo ORCID: 0000-0002-2514-2625, Pane-Farre, Christiane A., Pauli, Paul, Rief, Winfried, Strohle, Andreas, Plag, Jens, Lang, Thomas, Wittchen, Hans-Ulrich, Mattheisen, Manuel ORCID: 0000-0002-8442-493X, Meier, Sandra, Metspalu, Andres, Domschke, Katharina, Reif, Andreas, Hovatta, Iiris ORCID: 0000-0002-5990-7892, Lindefors, Nils, Andersson, Evelyn, Schalling, Martin, Mbarek, Hamdi ORCID: 0000-0002-1108-0371, Milaneschi, Yuri, de Geus, Eco J. C., Boomsma, Dorret, I, Penninx, Brenda W. J. H., Thorgeirsson, Thorgeir E., Steinberg, Stacy, Stefansson, Kari, Stefansson, Hreinn, Muller-Myhsok, Bertram, Hansen, Thomas Folkmann ORCID: 0000-0001-6703-7762, Borglum, Anders D., Werge, Thomas, Mortensen, Preben Bo, Nordentoft, Merete, Hougaard, David M., Hultman, Christina M., Sullivan, Patrick F., Nothen, Markus M., Woldbye, David P. D., Mors, Ole, Binder, Elisabeth B., Rueck, Christian, Ripke, Stephan, Deckert, Juergen and Schumacher, Johannes (2021). Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression. Mol. Psychiatr., 26 (8). S. 4179 - 4191. LONDON: SPRINGERNATURE. ISSN 1476-5578

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Abstract

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 x 10(-4) were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 x 10(-7)). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Forstner, Andreas J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Awasthi, SwapnilUNSPECIFIEDorcid.org/0000-0002-9692-8123UNSPECIFIED
Wolf, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maron, EduardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erhardt, AngelikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czamara, DarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eriksson, EliasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lavebratt, CatharinaUNSPECIFIEDorcid.org/0000-0003-4987-2718UNSPECIFIED
Allgulander, ChristerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedrich, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hecker, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rambau, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Conrad, RupertUNSPECIFIEDorcid.org/0000-0003-3207-2677UNSPECIFIED
Geiser, FranziskaUNSPECIFIEDorcid.org/0000-0002-4212-9692UNSPECIFIED
McMahon, Francis J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moebus, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hess, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buerfent, Benedikt C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herms, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heilmann-Heimbach, StefanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kockum, IngridUNSPECIFIEDorcid.org/0000-0002-0867-4726UNSPECIFIED
Olsson, TomasUNSPECIFIEDorcid.org/0000-0002-2938-1877UNSPECIFIED
Alfredsson, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alpers, Georg W.UNSPECIFIEDorcid.org/0000-0001-9896-5158UNSPECIFIED
Arolt, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fehm, LydiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fydrich, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlach, Alexander L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamm, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kircher, TiloUNSPECIFIEDorcid.org/0000-0002-2514-2625UNSPECIFIED
Pane-Farre, Christiane A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pauli, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rief, WinfriedUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strohle, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plag, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittchen, Hans-UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mattheisen, ManuelUNSPECIFIEDorcid.org/0000-0002-8442-493XUNSPECIFIED
Meier, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metspalu, AndresUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domschke, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hovatta, IirisUNSPECIFIEDorcid.org/0000-0002-5990-7892UNSPECIFIED
Lindefors, NilsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andersson, EvelynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schalling, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mbarek, HamdiUNSPECIFIEDorcid.org/0000-0002-1108-0371UNSPECIFIED
Milaneschi, YuriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Geus, Eco J. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boomsma, Dorret, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Penninx, Brenda W. J. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thorgeirsson, Thorgeir E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinberg, StacyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stefansson, KariUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stefansson, HreinnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller-Myhsok, BertramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hansen, Thomas FolkmannUNSPECIFIEDorcid.org/0000-0001-6703-7762UNSPECIFIED
Borglum, Anders D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Werge, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mortensen, Preben BoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordentoft, MereteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hougaard, David M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hultman, Christina M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sullivan, Patrick F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nothen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woldbye, David P. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mors, OleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Binder, Elisabeth B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rueck, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ripke, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deckert, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-607934
DOI: 10.1038/s41380-019-0590-2
Journal or Publication Title: Mol. Psychiatr.
Volume: 26
Number: 8
Page Range: S. 4179 - 4191
Date: 2021
Publisher: SPRINGERNATURE
Place of Publication: LONDON
ISSN: 1476-5578
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANXIETY; RISK; METAANALYSIS; AMYGDALAMultiple languages
Biochemistry & Molecular Biology; Neurosciences; PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60793

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