Max-Planck-Institute of Psychiatry, Munich, Germany.
Transl Psychiatry. 2012 Sep 4;2(9):e156. doi: 10.1038/tp.2012.85.
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 (n = 1670 cases and n = 2266 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 (n = 1038 cases and n = 2411 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 P = 1.4e-8 and P = 1.1e-8, 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.
一项最近针对惊恐障碍（PD）患者的全基因组关联研究发现，一个由两个单核苷酸多态性（SNPs）（rs7309727 和 rs11060369）组成的风险单倍型与 TMEM132D 基因的内含子 3 有关，该单倍型与三个独立样本中的 PD 相关。现在我们报告了一项后续确认研究，该研究使用了五个额外的 PD 病例对照样本（n = 1670 例病例和 n = 2266 例对照），这些样本是作为惊恐障碍国际联盟（PanIC）研究的一部分组装的，在分析中共有 2678 例病例和 3262 例对照。在新的欧洲血统（EA）独立样本中，rs7309727 和风险单倍型 rs7309727-rs11060369 的关联确实得到了复制，来自于原发性 PD 患者的信号最强，即没有主要精神共病的患者（n = 1038 例病例和 n = 2411 例对照）。这一发现与所有样本的荟萃分析结果相平行，在限制为 EA 原发性 PD 患者的样本中，风险单倍型和 rs7309727 分别达到了 P = 1.4e-8 和 P = 1.1e-8 的 P 值水平。在日本样本中，没有发现与 PD 相关的关联。目前的结果支持了最初的发现，即 TMEM132D 基因在 EA 个体中对 PD 的遗传易感性有贡献。我们的结果还表明，患者确定和遗传背景可能是改变这一关联信号在不同人群中的异质性的重要来源。
