Genetic variation in BDNF is associated with opioid use disorder severity

Abstract

As the opioid epidemic continues to challenge local communities in the United States, scientists, clinicians, and community stakeholders are seeking to understand the myriad factors that contribute to misuse in order to develop effective preventions and treatments. Among these efforts is the Camden Opioid Research Initiative (CORI) that aims to identify and characterize genetic and non-genetic risk factors for opioid use disorder (OUD). We explored potential genetic risk factors for OUD severity in four CORI study cohorts (N = 274) using a curated list of 116 candidate single nucleotide polymorphisms (SNPs) previously implicated in opioid dependence. Our results replicate one SNP, rs13306221, in the BDNF gene, as having a significant association with OUD severity. Rs13306221 and a second SNP in strong linkage disequilibrium that is also associated with OUD severity, rs56164415, both lie in an open chromatin domain near the BDNF transcription start site. The rs13306221 genotype associated with increased OUD severity is additionally associated with reduced BDNF expression in lymphoblastoid cell lines consistent with a functional role in BDNF regulation.