Deep resequencing of 17 glutamate system genes identifies rare variants in DISC1 and GRIN2B affecting risk of opioid dependence.

ABSTRACT: The N-methyl-D-aspartate (NMDA) glutamate receptors play important roles in the pathophysiology of substance dependence (SD), but no strong genetic evidence has associated common variants in NMDAR-related genes to SD. We hypothesized that rare variants (RVs) with minor allele frequency <1% in the NMDAR-related genes might exert large effects on SD risk. We sequenced 34 544 bp of coding and flanking intronic regions of 17 genes involved in the NMDA system in 760 subjects, all with co-occurring alcohol dependence, cocaine dependence and opioid dependence (OD), and 760 healthy control subjects. One hundred percent of the target regions were sequenced at >1000× coverage. We identified 454 variants, including 380 RVs. Based on case-control allele count differences, we genotyped 11 exonic RVs in

SUBMITTER: Xie P 

PROVIDER: S-EPMC3815683 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature