ABSTRACT

Background and objectives

Anxiety sensitivity (AS) refers to a fear of the negative implications of anxiety, and arises due to gene-environment interactions. We investigated whether genetic variation in two neuropeptides implicated in the stress response, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide receptor 1, interacted with childhood trauma (CT) to influence AS.

Design and methods

This cross-sectional study examined the CT x genetic variant effects on AS in 951 adolescents who self-identified as Xhosa or South African Colored (SAC) ethnicity.

Results

In Xhosa females, the NPY rs5573 A allele and rs3037354 deletion variant were associated with increased (p = 0.035) and decreased (p = 0.034) AS, respectively. The interaction of CT and the NPY rs5574 A allele increased AS in SAC female participants (p = 0.043). The rs3037354 deletion variant protected against AS with increased CT in SAC male participants (p = 0.011).

Conclusions

The NPY rs5574 A allele and rs3037354 deletion variant interact with CT to act as risk and protective factors, respectively, for AS in an ethnicity- and sex- differentiated manner. Our results reaffirm the role of NPY and gene-environment interactions in anxiety-related behaviors and reinforce the need for psychiatric genetics studies in diverse populations.

中文翻译：

---

神经肽 Y 的遗传变异与童年创伤相互作用以影响焦虑敏感性

摘要

背景和目标

焦虑敏感性（AS）是指对焦虑负面影响的恐惧，是由于基因-环境相互作用而产生的。我们研究了与应激反应有关的两种神经肽、神经肽 Y (NPY) 和垂体腺苷酸环化酶激活多肽受体 1 的遗传变异是否与儿童创伤 (CT) 相互作用以影响 AS。

设计和方法

这项横断面研究检查了 951 名自称为科萨人或南非有色人种 (SAC) 的青少年的 CT x 基因变异对 AS 的影响。

结果

在科萨女性中，NPY rs5573 A 等位基因和 rs3037354 缺失变异分别与增加 ( p  = 0.035) 和减少 ( p  = 0.034) AS 相关。CT 和NPY rs5574 A 等位基因的相互作用增加了 SAC 女性参与者的 AS（p  = 0.043）。在 SAC 男性参与者中，rs3037354 缺失变体对 AS 具有保护作用，CT 增加（p  = 0.011）。

结论

NPY rs5574 A 等位基因和 rs3037354 缺失变体与 CT 相互作用，分别以种族和性别区分的方式作为 AS 的风险和保护因素。我们的结果重申了 NPY 和基因-环境相互作用在焦虑相关行为中的作用，并加强了对不同人群进行精神遗传学研究的必要性。