The Genetic Structure of Pain in Depression Patients: A Genome-Wide Association Study and Proteome-Wide Association Study
Abstract Background Pain symptoms are common in the patients with depression. Comparing with the general population, the pain in depression patients has more complex biological mechanism. We aim to explore the etiological mechanism of pain in depression patients from the perspective of genetics. Methods Utilizing the UK Biobank samples with self-reported depression status or PHQ score ≥10, we conducted genome-wide association study (GWAS) of seven pain traits (N=1,133-58,349). The GWAS summary were then integrated with two different reference protein weights (ROS/MAP and Banner) for proteome-wide association study (PWAS) using the FUSION pipeline. Additionally, LDSC analysis was performed to explore the genetic correlation between pain traits in depression patients and common psychiatry disorders. And biological processes and functions that related to pain associated genes in depression patients were analyzed by gene set enrichment analysis. Results GWAS identified 3 significant genes associated with different pain traits in depression patients, including TRIOBP (PGWAS= 4.48× 10−8) for stomach or abdominal pain, SLC9A9(PGWAS= 2.77× 10−8) for multisite chronic pain (MCP) and ADGRF1 (PGWAS= 1.51× 10−8) for neck or shoulder pain. PWAS also identified multiple candidate genes associated with different pain traits in depression patients, such as TPRG1L (permutation-based PPWAS−Banner= 3.38× 10−2) and SIRPA (permutation-based PPWAS−Banner= 3.65×10−2) for MCP etc. LDSC analysis results showed that MCP was positively correlated with attention-deficit hyperactivity disorder (ADHD) (genetic correlation(rg) = 0.123, PLDSC = 0.039) and post-traumatic stress disorder (PTSD) (rg = 0.217, PLDSC = 0.029). Conclusions We reported multiple novel candidate genes and genetic correlations for pain traits in depression patients, providing novel clues for understanding the genetic mechanisms underlying the pain in depression patients.