Pharmacogenetics of stimulant abuse liability: association of CDH13 variant with amphetamine response in a racially-heterogeneous sample of healthy young adults.

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A previous genome-wide association study (GWAS) in a predominately Caucasian sample of healthy young adults linked greater amphetamine-induced rewarding effects with the rs3784943 G allele of the cadherin 13 (CDH13; i.e., a cell adhesion molecule implicated in neuronal connectivity) gene. This association has not been subsequently examined, nor has it been studied in Asian populations, which may have greater frequencies of the risk allele. The objective of this study was to examine the association of rs3784943 with amphetamine response in a racially heterogeneous sample (37% Asian) of healthy young adults. Participants (N=84; 18-35years old) genotyped for rs3784943 completed counterbalanced sessions involving 20mg oral d-amphetamine or placebo administration. At both sessions, cardiovascular and subjective drug effects measures were collected. In the combined racially heterogeneous sample, amphetamine (vs. placebo) effects were significantly greater on "Feel Drug" ratings (p<0.05) and marginally greater on "Feel High" ratings and systolic blood pressure (p<0.10) in G/A + G/G genotypes than A/A genotypes. The G allele was more common among Asian than other racial groups. Among the subsample of Asian participants (N=31), drug effects were significantly greater on Feel Drug (p<0.05) and marginally greater on Feel High and heart rate (p<0.10) among Asians with G/A + G/G (vs. A/A) genotypes. In concert with a previous GWAS result, this candidate gene study provides convergent evidence implicating CDH13 rs3784943 variant in d-amphetamine's drug effect profile and suggests generalization to Asian populations. CDH13 and genes coding for other cell adhesion molecules may be worthy of study in the biology of psychostimulant abuse liability.