the biobank of the PKU newborn screening program at the National Genetic Laboratory in Sofia (250,000 samples, > 85% of all live births since 1998). Given the low prevalence of heroin dependence in the population (under 1%), the use of population controls is not expected to result in a loss of statistical power. The study was conducted with approvals from the IRBs of Washington University in Saint Louis and the Medical University in Sofia. All participants gave informed consent.