Genetic variation in neuropeptide Y interacts with childhood trauma to influence anxiety sensitivity

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.

KEYWORDS:

• Anxiety
• childhood trauma
• gene-environment
• genetics
• neuropeptide Y
• pituitary adenylate cyclase-activating polypeptide

Acknowledgements

Thanks to Rob Sinnerton for presentation of the data at the 2018 European College of Neuropsychopharmacology meeting.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is based upon research supported by the South African Research Chair in PTSD from the Department of Science and Technology and the National Research Foundation (JSW, SMJH, SS) as well as a South African Medical Research Council “SHARED ROOTS” Flagship Project, grant MRC-RFA-IFSP-01-2013/SHARED ROOTS (SMJH, SS). Research reported in this publication was partly supported by the South African Medical Research Council. The funding bodies were not involved in the design of the study; the collection, analysis, or interpretation of data; or in the writing of the manuscript.