This project seeks to uncover patterns in pain comorbidity and explore underlying mechanisms, leveraging brain imaging and OMICs methodologies. In addition to UK Biobank (UKBB), we utilize complimentary data from the Tromsø Study and Fit Futures Study in Norway and Rotterdam Study in the Netherlands, which also include Quantitative Sensory Tests (QST) of pain sensitivity. The project is an extension of the Horizon 2020 project PainFACT (grant #848099).
Key objectives include:
1. Comorbidity patterns: We aim to map chronic pain and its comorbidities, assessing relationship strength and temporal order. Analyses will also assess to what extent lifestyle and demographic risk factors confound these relationships.
2. Brain Imaging Signatures: We will identify brain imaging signatures for chronic pain and QST, and examine whether these signatures are associated with pain comorbidities, indicating common central nervous pathways linking pain with these conditions.
3. Protein Risk Scores: Using a broad unbiased panel of proteins, we aim to map molecular pathways associated with pain phenotypes. We will develop protein risk scores for QST and chronic pain, and test whether these protein risk scores are predictive of comorbid conditions, indicating possible shared etiology.
4. Genetic association studies (GWAS): We conduct GWAS to identify genetic variants associated with QST, chronic pain, key comorbidities, associated brain signatures, and protein scores. From these we will generate polygenic risk scores used as instrumental variables in Objective 5.
5. Genetic Correlations and Mendelian Randomization: Utilizing summary statistics from Objective 4 and other GWAS studies, we will estimate genetic correlations and test causal relationships with bi-directional Mendelian randomization analysis, between pain phenotypes, key comorbidities, imaging signatures, and protein profiles.