Chronic overlapping pain conditions (COPCs) are believed to share common etiological mechanisms involving central sensitization. Genetic and environmental factors putatively combine to influence susceptibility to central sensitization and COPCs. This study employed a genome-wide polygenic risk score approach to evaluate genetic influences on 8 common COPCs. COPCs were identified by ICD codes in Vanderbilt’s de-identified clinical biorepository (BioVU), with each COPC condition empirically weighted for level of central sensitization based on prior work. A centralized pain score was calculated for 55,340 individuals by summing the weighted number of COPCs. Overall, 12,502 individuals (22.6%) were diagnosed with at least one COPC, with females exhibiting nearly twice the mean centralized pain score as males. To assess genetic influence on centralized pain in COPCs, 6 pain polygenic risk scores (PRSs) were developed using UK Biobank data to predict 6 pain criteria (no pain, neck/shoulder, abdomen, hip, knee, low back pain). These PRSs were then deployed in the BioVU cohort to test for association with centralized pain scores. In regression models adjusted for age, sex, and BMI, all pain PRSs except hip pain were significantly associated with centralized pain scores. Our findings support a shared polygenic influence across COPCs potentially involving central sensitization mechanisms. PERSPECTIVE: This study used a polygenic risk score approach to investigate genetic influences on chronic overlapping pain conditions. Significant findings in this study provide evidence supporting previous hypotheses that a shared polygenic influence involving central sensitization may underly chronic overlapping pain conditions, and can guide future biomarker and risk assessment research.