The use of the minor allele frequencies in the NHLBI-ESP database as a ‘control’ cohort for our association analyses could also be a limitation of this study. The individuals which comprise this sample are taken from population based cohorts, only some of which are screened for drug addiction. In 2008–2009 only 1.9% of the United States population was classed as dependent on an illicit drug (National Survey on Drug Use and Health, 2010) and only a subset were addicted to heroin or cocaine. The NHLBI-ESP controls may, therefore, include some drug addicted individuals. However, the addicted cohort will be enriched for addiction risk alleles compared to population based cohorts.