Replication and meta-analysis of TMEM132D gene variants in panic disorder.

TY - JOUR

T1 - Replication and meta-analysis of TMEM132D gene variants in panic disorder.

AU - Erhardt, A

AU - Akula, N

AU - Schumacher, J

AU - Czamara, D

AU - Karabalai, N

AU - Müller-Myhsok, B

AU - Mors, O

AU - Borglum, A

AU - Kristensen, AS

AU - Woldbye, David Paul Drucker

AU - Koefoed, Pernille

AU - Eriksson, E

AU - Maron, E

AU - Metspalu, A

AU - Nurnberger, J

AU - Philibert, RA

AU - Kennedy, J

AU - Domschke, K

AU - Reif, A

AU - Deckert, J

AU - Otowa, T

AU - Kawamura, Y

AU - Kaiya, H

AU - Okazaki, Y

AU - Tanil, H

AU - Tokunaga, K

AU - Sasaki, T

AU - Ioannidis, JPA

AU - McMahon, FJ

AU - Binder, EB

PY - 2012

Y1 - 2012

N2 - A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case-control samples (n1670 cases and n2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n1038 cases and n2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P1.4e8 and P1.1e8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations.

AB - A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case-control samples (n1670 cases and n2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n1038 cases and n2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P1.4e8 and P1.1e8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations.

U2 - 10.1038/tp.2012.85

DO - 10.1038/tp.2012.85

M3 - Journal article

C2 - 22948381

SN - 2158-3188

VL - 2:e156

JO - Translational Psychiatry

JF - Translational Psychiatry

ER -