The opioid system has important roles in both antinociception and reward.1, 2 Therefore, opioids, such as morphine and fentanyl, are widely used not only as effective analgesics for the treatment of acute and chronic pain but also as abused drugs. The opioid system is also involved in the rewarding effects of morphine,3 ethanol,4 cocaine,5 and various other drugs6, 7, 8 or behaviors. However, opioid sensitivity is well known to vary widely among individual subjects,9 resulting in differences in the effectiveness of opioid analgesics and vulnerability to dependence on opioids and other drugs or behaviors. Individual differences may be attributable to both genetic and environmental factors,10 although the relative influence of each of these factors can be diverse. To date, several candidate genetic polymorphisms have been reported to be associated with opioid sensitivity in human studies.10, 11, 12, 13, 14 However, such polymorphisms have not sufficiently explained the wide range of interindividual variance observed in the sensitivity to opioid analgesics. A genome-wide approach has not yet been adopted to explore the best candidates, although this approach has been applied to other
