Phenome-Wide Association Study of P2RX7 Identifies Schizophrenia and Mood Disorders as Primary Associated Phenotypes

Author(s)

• Ling Zhu
• Qiao Mao
• Zhixiong Luo
• Bin Chen
• Yong Zhang
• Xiaowei Lu
• Ping Liu
• Jiawu Ji
• Xiaoping Wang
• Kesheng Wang PhD, MA, BS, University of South Carolina, College of Nursing, Columbia, South Carolina.Follow
• Xinghua Pan
• Yuping Cao
• Na Liu
• Jennifer Luo
• Lingjun Zuo
• Zhiren Wang
• Xingguang Luo
• Xiaoyun Guo

Document Type

Article

Abstract

Objectives: P2RX7 has been implicated in bipolar disorder, major depressive disorder, schizophrenia, anxiety disorders, Alzheimer's disease, and Parkinson's disease. However, the specificity and comparability of these as sociations remain unclear. This study aimed to systematically evaluate multiple neuropsychiatric disorders to identify those most robustly associated with P2RX7.

Methods: We analyzed 1861 imputed SNPs spanning the P2RX7 gene in 1,087,925 individuals from 72 inde pendent cohorts across 18 neuropsychiatric disorders. SNP-disease associations were assessed within each cohort, followed by meta-analysis and false discovery rate (FDR) correction to identify significant disease-risk variants. P2RX7 mRNA and protein expression across tissues or cells was characterized. Functional analyses evaluated the regulatory effects of disease-associated SNPs on P2RX7 mRNA expression, subcortical gray matter volumes (GMVs), cortical surface area (SA), and cortical thickness (TH).

Results: Bipolar disorder showed the strongest association with P2RX7 variants in European Americans (EAs) (4.0 ×10^-8 ≤p ≤0.004; 3.8 ×10^-5 ≤q ≤0.05), followed by schizophrenia in EAs (8.9 ×10^-6 ≤p ≤2.6 × 10^-4; 9.4 ×10^-3 ≤q ≤0.043)  and Chinese populations (2.1 ×10^-5 ≤p ≤1.7 ×10^-3; 6.8 ×10^-3 ≤q ≤0.049), and major depression in both EAs (p =4.1 ×10^-5; q =0.030) and Chinese (4.3 ×10^-5 ≤p ≤0.009; 6.1 ×10^-3

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.jad.2026.121327

Publication Info

Published in Journal of Affective Disorders, Volume 402, 2026, pages 121327-.

Rights

© 2026 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

APA Citation

Zhu, L., Mao, Q., Luo, Z., Chen, B., Zhang, Y., Lu, X., Liu, P., Ji, J., Wang, X., Wang, K., Pan, X., Cao, Y., Liu, N., Zheng, J., Wang, F., Yang, K., Yang, F., Yu, Z., Hu, J., & Luo, J. (2026). Phenome-wide association study of P2RX7 identifies schizophrenia and mood disorders as primary associated phenotypes. Journal of Affective Disorders, 402, 121327.https://doi.org/10.1016/j.jad.2026.121327