The Consequence of Concomitantly Present Functional Genetic Variants for the Identification of Functional Genotype–Phenotype Associations in Pain

Genetics‐based personalized approaches to pain management have received a setback because of the nonreproducibility of functional genetic associations such as the pain‐modulatory effect 1 , 2 of the catechol‐O‐methyl transferase ( COMT ) gene 472G>A single‐nucleotide polymorphism. 3 , 4 Given that many of the pain‐relevant genetic variants are common (allelic frequencies of 10–50%), we hypothesized that a major reason for difficulties in reproducing demonstrations of genetic influences on pain is the concomitant presence in a single individual of several functional genetic polymorphisms that act as confounders. Clinical Pharmacology & Therapeutics (2008); 85 , 1, 25–30 doi: 10.1038/clpt.2008.103