The rs10692285 polymorphism within the 3′UTR of RYR2 confer SUD risk. The genotype of rs10692285 was associated with RYR2 expression level. rs10692285 could alter local structure of RYR2 mRNA and microRNA binding. rs10692285 may become a potential marker for molecular diagnosis of SUD. Abnormal ion channel activity is very likely involved in SUD.