Hohoff, Christa, Weber, Heike ORCID: 0000-0002-9421-1292, Richter, Jan ORCID: 0000-0002-7127-6990, Domschke, Katharina, Zwanzger, Peter M., Ohrmann, Patricia, Bauer, Jochen, Suslow, Thomas ORCID: 0000-0003-4560-0555, Kugel, Harald ORCID: 0000-0002-4349-1984, Baumann, Christian, Klauke, Benedikt, Jacob, Christian P., Fritze, Juergen, Bandelow, Borwin ORCID: 0000-0003-2511-3768, Gloster, Andrew T., Gerlach, Alexander L. ORCID: 0000-0001-6794-5349, Kircher, Tilo ORCID: 0000-0002-2514-2625, Lang, Thomas, Alpers, Georg W., Stroehle, Andreas, Fehm, Lydia ORCID: 0000-0002-0825-8466, Wittchen, Hans-Ulrich ORCID: 0000-0002-6311-7711, Arolt, Volker, Pauli, Paul ORCID: 0000-0003-0692-6720, Hamm, Alfons, Reif, Andreas and Deckert, Juergen (2015). RGS2 Genetic Variation: Association Analysis with Panic Disorder and Dimensional as Well as Intermediate Phenotypes of Anxiety. Am. J. Med. Genet. B, 168 (3). S. 211 - 223. HOBOKEN: WILEY. ISSN 1552-485X

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Abstract

Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P=0.006 and P=0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P=0.015) and showed significantly more defensive behavior during fear provoking situations (P=0.001). Furthermore, significant effects on brain activation in response to angry (P=0.013), happy (P=0.042) and neutral faces (P=0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD. (c) 2015 Wiley Periodicals, Inc.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hohoff, ChristaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, HeikeUNSPECIFIEDorcid.org/0000-0002-9421-1292UNSPECIFIED
Richter, JanUNSPECIFIEDorcid.org/0000-0002-7127-6990UNSPECIFIED
Domschke, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zwanzger, Peter M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ohrmann, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bauer, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suslow, ThomasUNSPECIFIEDorcid.org/0000-0003-4560-0555UNSPECIFIED
Kugel, HaraldUNSPECIFIEDorcid.org/0000-0002-4349-1984UNSPECIFIED
Baumann, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klauke, BenediktUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jacob, Christian P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritze, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bandelow, BorwinUNSPECIFIEDorcid.org/0000-0003-2511-3768UNSPECIFIED
Gloster, Andrew T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlach, Alexander L.UNSPECIFIEDorcid.org/0000-0001-6794-5349UNSPECIFIED
Kircher, TiloUNSPECIFIEDorcid.org/0000-0002-2514-2625UNSPECIFIED
Lang, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alpers, Georg W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroehle, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fehm, LydiaUNSPECIFIEDorcid.org/0000-0002-0825-8466UNSPECIFIED
Wittchen, Hans-UlrichUNSPECIFIEDorcid.org/0000-0002-6311-7711UNSPECIFIED
Arolt, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pauli, PaulUNSPECIFIEDorcid.org/0000-0003-0692-6720UNSPECIFIED
Hamm, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deckert, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-403939
DOI: 10.1002/ajmg.b.32299
Journal or Publication Title: Am. J. Med. Genet. B
Volume: 168
Number: 3
Page Range: S. 211 - 223
Date: 2015
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1552-485X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; CENTRAL-NERVOUS-SYSTEM; JAPANESE POPULATION; PREFRONTAL CORTEX; TRANSCRIPTION FACTOR; AGORAPHOBIA; EXPRESSION; AMYGDALA; BRAINMultiple languages
Genetics & Heredity; PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/40393

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