The interaction between chronic pain and genetics in contributing to cognitive impairment

Objective

Chronic pain (CP), defined as pain lasting more than three months, affects ~30% of the global population. Emerging evidence indicates that CP increases the risk of cognitive impairments, posing a major challenge for rapidly aging societies. However, it remains unclear which individuals with CP are most vulnerable, limiting precision prevention and targeted intervention. This project will conduct the first genome-wide investigation of how genetic predisposition modifies the cognitive consequences of CP. It will (i) identify genetic subgroups at high risk of CP-related cognitive impairment; (ii) uncover proteomic and metabolomic alterations underlying this gene-CP interaction, exploring opportunities for drug repurposing and lifestyle recommendations for the confirmed high-risk subgroup; and (iii) test whether the mediating effect of brain aging acceleration on the CP-cognition link is moderated by genetic predisposition. Building on my prior work demonstrating the CP–cognition association (published in PNAS, Nature Mental Health, and TICS), this project moves decisively from observation to mechanistic and translational insight. It goes beyond the state-of-the-art by leveraging large-scale cohorts (UK Biobank, HUNT) and integrating genetics, multi-omics, neuroimaging, and artificial intelligence within a unified framework. This fellowship is designed to be a transformative career step. The two-way knowledge exchange with the host, combined with specialized training during the secondment, will strengthen my interdisciplinary expertise, leadership capacity, and project management skills. This will provide the crucial foundation to transition into an independent research leader and secure future collaborative funding, ultimately translating today's discoveries into tomorrow's clinical solutions.