rs1133503

This association study of 3,992 individuals from 2 family-based and 2 case-control samples examined the MANEA gene variants in relation to cocaine dependence (CD) and cocaine-induced paranoia (CIP). The rs9387522 A allele in the 3' untranslated region was associated with increased risk of CIP across all 4 data sets (P < 0.001), with strongest evidence for CIP associations in the MANEA promoter and coding regions (P < 0.001). Haplotype analysis identified the T-T-A and C-T-A haplotypes as conferring increased CIP risk while C-A-C haplotype decreased risk, suggesting the functional variant likely resides in the MANEA promoter or 3' UTR region.

Family-based genome-wide association study of substance dependence in 1,699 subjects from 673 families (339 African American, 334 European American families) using 5,633 SNP markers. The study identified 56 significant associations across cocaine dependence, opioid dependence, nicotine dependence, alcohol dependence, and cocaine-induced paranoia. The strongest association was rs1133503 in MANEA gene with cocaine-induced paranoia (p=0.00005). Other notable findings include associations between NAV3 and opioid dependence, SYT13 and cocaine dependence, and PLEKHG1 with nicotine dependence scores.