studied. In an accumulation of evidence for rs1799971, meta-analysis of >28,000 European ancestry participants from 25 studies supported a modest association with general substance dependence, rather than opioids or any substance specifically [113]. As we previously reported, the cis-eQTL SNP rs3778150 may explain the prior inconsistent associations, as the rs1799971-A allele conferred increased heroin addiction risk only in the presence of the rs3778150-C allele that lowers OPRM1 expression levels and plausibly disrupts the opioid system of a key compensatory response to exogenous opioid exposure [112]. The association pattern observed between heroin addiction and the haplotype carrying rs3778150-C and rs1799971-A has been extended to subjective alcohol response [114].
