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The purpose of this study was to examine genetic variability and knee pain in persons with osteoarthritis (OA). Seventy-five participants with medial compartment knee OA were recruited from a large Midwestern tertiary care center. Participants exhibited a mean age of 56.3 years; females comprised 61% of the sample. Measures of pain included subjective pain intensity at rest and with movement, cutaneous mechanical sensation and pain testing, heat pain threshold, and pressure pain threshold. Seventy-four participants were genotyped for 25 genetic variants across 15 candidate genes for central or peripheral pain pathways. Analysis suggests a role for four genes (EDNRA, COMT, BDRKB1, and IL1B) in several components of pain in persons with knee OA. The results from this study will help guide the development and evaluation of tailored strategies to decrease pain, improve function, and prevent the development of new chronic pain syndromes in older adults experiencing OA. [Research in Gerontological Nursing, xx(x), xx-xx.].