Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).

Elation (POMS) example phenotype.Panel A shows the mean (SEM) scores on the POMS Elation scale at each time point before and after administration of placebo or d-amphetamine (10 and 20 mg). The box identifies the values shown in greater detail in Panel B. Panel B shows a boxplot of the Elation phenotype at 90 minutes after placebo, 10 or 20 mg d-amphetamine sessions. Panel C shows the Pearson correlation coefficient for the Elation phenotypes at all six time points for the 20 mg session: darker blue indicates high correlation and white indicates low correlation.

Potential association of rs3784943 (CDH13) with an amphetamine response factor.Panel A shows the factor loadings for factor F1; abbreviations of outcome measures are defined in the text. Panel B shows the raw phenotype scores as a function of dose (denoted by color coded vertically stacked panels) and time (x-axis within each panel) for individuals in the upper and lower deciles of this factor. Panel C shows the association between factor F1 and each SNP (expressed as −log10 P), the most significant association was on chromosome 16 at rs3784943 (P = 4.58×10−8). The red horizontal line indicates 5×10−8, which is often used as a threshold for significance. The blue horizontal line indicates 1×10−5, which could be considered a threshold for suggestive evidence. Panel D shows a Q-Q plot of observed −log10 P versus the average −log10 P from ten random permutations. Panel E shows a boxplot of the values for factor F1 stratified by genotype. The width of each box corresponds to number of observations at the corresponding genotype. Panel F shows the raw phenotype scores stratified by genotypes as a function of dose and time. Asterisks indicate a significant Drug×time×genotype interaction in a 3×3×6 repeated measures ANOVA using age, sex, BMI, and the first two principal components as covariates. * P≤0.05; ** P≤0.01; *** P≤0.0001; **** P≤10−4.

Potential association of rs472402 (SRD5A1) with the positive affect baseline factor.Panel A shows the factor loadings for factor F2; abbreviations of outcome measures are defined in the text. Panel B shows the raw phenotype scores as a function of dose (denoted by color coded vertically stacked panels) and time (x-axis within each panel) for individuals in the upper and lower deciles of this factor. Panel C shows the association between factor F1 and each SNP (expressed as −log10 P), the most significant association was on chromosome 5 at rs472402 (P = 2.53×10−7). The red horizontal line indicates 5×10−8, which is often used as a threshold for significance. The blue horizontal line indicates 1×10−5, which could be considered a threshold for suggestive evidence. Panel D shows a Q-Q plot of observed −log10 P versus the average −log10 P from ten random permutations. Panel E shows a boxplot of the values for factor F1 stratified by genotype. The width of each box corresponds to number of observations at the corresponding genotype. Panel F shows the raw phenotype scores stratified by genotypes as a function of dose and time. Asterisks indicate a significant main effect of genotype in a 3×3×6 repeated measures ANOVA using age, sex, BMI, and the first two principal components as covariates. * P≤0.05; **** P≤10−4.