Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression
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 comprisi...
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Format: | Article in Journal/Newspaper |
Language: | English |
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SPRINGERNATURE
2021
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Online Access: | https://kups.ub.uni-koeln.de/60793/ |
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ftubkoeln:oai:USBKOELN.ub.uni-koeln.de:60793 |
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Open Polar |
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Cologne University: KUPS |
op_collection_id |
ftubkoeln |
language |
English |
topic |
ddc:no |
spellingShingle |
ddc:no Forstner, Andreas J. Awasthi, Swapnil Wolf, Christiane Maron, Eduard Erhardt, Angelika Czamara, Darina Eriksson, Elias Lavebratt, Catharina Allgulander, Christer Friedrich, Nina Becker, Jessica Hecker, Julian Rambau, Stefanie Conrad, Rupert Geiser, Franziska McMahon, Francis J. Moebus, Susanne Hess, Timo Buerfent, Benedikt C. Hoffmann, Per Herms, Stefan Heilmann-Heimbach, Stefanie Kockum, Ingrid Olsson, Tomas Alfredsson, Lars Weber, Heike Alpers, Georg W. Arolt, Volker Fehm, Lydia Fydrich, Thomas Gerlach, Alexander L. Hamm, Alfons Kircher, Tilo Pane-Farre, Christiane A. Pauli, Paul Rief, Winfried Strohle, Andreas Plag, Jens Lang, Thomas Wittchen, Hans-Ulrich Mattheisen, Manuel Meier, Sandra Metspalu, Andres Domschke, Katharina Reif, Andreas Hovatta, Iiris Lindefors, Nils Andersson, Evelyn Schalling, Martin Mbarek, Hamdi Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression |
topic_facet |
ddc:no |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Forstner, Andreas J. Awasthi, Swapnil Wolf, Christiane Maron, Eduard Erhardt, Angelika Czamara, Darina Eriksson, Elias Lavebratt, Catharina Allgulander, Christer Friedrich, Nina Becker, Jessica Hecker, Julian Rambau, Stefanie Conrad, Rupert Geiser, Franziska McMahon, Francis J. Moebus, Susanne Hess, Timo Buerfent, Benedikt C. Hoffmann, Per Herms, Stefan Heilmann-Heimbach, Stefanie Kockum, Ingrid Olsson, Tomas Alfredsson, Lars Weber, Heike Alpers, Georg W. Arolt, Volker Fehm, Lydia Fydrich, Thomas Gerlach, Alexander L. Hamm, Alfons Kircher, Tilo Pane-Farre, Christiane A. Pauli, Paul Rief, Winfried Strohle, Andreas Plag, Jens Lang, Thomas Wittchen, Hans-Ulrich Mattheisen, Manuel Meier, Sandra Metspalu, Andres Domschke, Katharina Reif, Andreas Hovatta, Iiris Lindefors, Nils Andersson, Evelyn Schalling, Martin Mbarek, Hamdi |
author_facet |
Forstner, Andreas J. Awasthi, Swapnil Wolf, Christiane Maron, Eduard Erhardt, Angelika Czamara, Darina Eriksson, Elias Lavebratt, Catharina Allgulander, Christer Friedrich, Nina Becker, Jessica Hecker, Julian Rambau, Stefanie Conrad, Rupert Geiser, Franziska McMahon, Francis J. Moebus, Susanne Hess, Timo Buerfent, Benedikt C. Hoffmann, Per Herms, Stefan Heilmann-Heimbach, Stefanie Kockum, Ingrid Olsson, Tomas Alfredsson, Lars Weber, Heike Alpers, Georg W. Arolt, Volker Fehm, Lydia Fydrich, Thomas Gerlach, Alexander L. Hamm, Alfons Kircher, Tilo Pane-Farre, Christiane A. Pauli, Paul Rief, Winfried Strohle, Andreas Plag, Jens Lang, Thomas Wittchen, Hans-Ulrich Mattheisen, Manuel Meier, Sandra Metspalu, Andres Domschke, Katharina Reif, Andreas Hovatta, Iiris Lindefors, Nils Andersson, Evelyn Schalling, Martin Mbarek, Hamdi |
author_sort |
Forstner, Andreas J. |
title |
Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression |
title_short |
Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression |
title_full |
Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression |
title_fullStr |
Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression |
title_full_unstemmed |
Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression |
title_sort |
genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression |
publisher |
SPRINGERNATURE |
publishDate |
2021 |
url |
https://kups.ub.uni-koeln.de/60793/ |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
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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1766041656345231360 |
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ftubkoeln:oai:USBKOELN.ub.uni-koeln.de:60793 2023-05-15T16:51:32+02:00 Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression Forstner, Andreas J. Awasthi, Swapnil Wolf, Christiane Maron, Eduard Erhardt, Angelika Czamara, Darina Eriksson, Elias Lavebratt, Catharina Allgulander, Christer Friedrich, Nina Becker, Jessica Hecker, Julian Rambau, Stefanie Conrad, Rupert Geiser, Franziska McMahon, Francis J. Moebus, Susanne Hess, Timo Buerfent, Benedikt C. Hoffmann, Per Herms, Stefan Heilmann-Heimbach, Stefanie Kockum, Ingrid Olsson, Tomas Alfredsson, Lars Weber, Heike Alpers, Georg W. Arolt, Volker Fehm, Lydia Fydrich, Thomas Gerlach, Alexander L. Hamm, Alfons Kircher, Tilo Pane-Farre, Christiane A. Pauli, Paul Rief, Winfried Strohle, Andreas Plag, Jens Lang, Thomas Wittchen, Hans-Ulrich Mattheisen, Manuel Meier, Sandra Metspalu, Andres Domschke, Katharina Reif, Andreas Hovatta, Iiris Lindefors, Nils Andersson, Evelyn Schalling, Martin Mbarek, Hamdi 2021 https://kups.ub.uni-koeln.de/60793/ eng eng SPRINGERNATURE 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 ddc:no doc-type:article publishedVersion 2021 ftubkoeln 2022-11-09T07:35:08Z 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. Article in Journal/Newspaper Iceland Cologne University: KUPS |