There is also an interplay between use of medically indicated or recreationally used prescription opioids or heroin in determining who develops OD. Prescription opioids used for pain relief are generally safe when taken for a short time and as prescribed by a doctor. In a U.S. veteran population, individuals who used prescription opioids recreationally had 19 times the odds of initiating heroin use, fewer than four percent of people who abuse prescription opioids initiate using heroin within five years [25]. Despite our inability to distinguish between disease course with regard to specific opioids and their pattern of initiation, these related phenotypes have two properties that make them attractive for variant discovery: namely (1) they do not include individuals who were never exposed to opioids or cocaine and (2) they may be better indicators of an individual’s genetic risk for OD/CD than case-control status because they distinguish between cases who develop the disorder slowly (i.e. are more genetically resistant) and those who develop it rapidly (i.e. are highly genetically susceptible), assuming these differences are partially under genetic control.
