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Identifying Candidate Proteins and Chemicals for Age at First Episode of Depression and Postpartum Depression

Feng Zhang*, Na Zhang, Zhen Zhang, Shiqiang Cheng, Yumeng Jia, Yan Wen, Xiaoyue Qin, Dan He, Wenming Wei, Yijing Zhao, Qingqing Cai, Sirong Shi, Xiaoge Chu

Background: Depression is not only the leading cause of disability worldwide. Limited studies have been conducted to explore the proteins and chemicals associated with Age at First Episode of Depression (AFED) and Postpartum Depression (PPD) from genetic perspective.

Methods: The Polygenic Risk Score (PRS) of 130 brain proteins, 262 plasma proteins and 404 Cerebro Spinal Fluid (CSF) proteins were first calculated utilizing the genotype data from the UK Biobank. Pearson correlation analysis was then conducted to test the association of each protein PRS with AFED and PPD in UK Biobank. Based on chemical-gene interaction data of The Comparative Toxicogenomics Database (CTD), we also conducted enrichment analysis to identify the chemicals associated with depression-related proteins.

Results: Pearson correlation analysis identified 40 candidate proteins associated with AFED, such as IGFBP-7 (P=3.17 × 10-2 , Brain Protein), MIC-1 (P=1.25 × 10³ Plasma Protein), 18 candidate proteins associated with PPD, such as TNFSF15 (P=6.44 × 10^-4, CSF Protein), IL1R1 (P=1.17 × 10^-2, CSF Protein), ART (P=1.2310-2, CSF Protein). Among 10,103 analyzed chemicals, enrichment analysis identified 43 chemicals for AFED and 13 chemicals for PPD, such as Pirinixic acid (P=7.50 × 10^-4, Brian Protein) for AFED, Benzo (e) pyrene (P=7.1 × 10^-3, Brain Protein) for PPD.

Conclusion: Our study identified multiple candidate proteins and chemicals associated with depression traits, which provides new clues for exploring the pathogenesis, and may serve as new targets for the treatment of AFED and PPD.