Multivariate analysis of subjective responses to d-amphetamine in healthy volunteers finds novel genetic pathway associations

Rationale Researchers studying behavioral and physiologic effects of d -amphetamine have explored individual response differences to the drug. Concurrently, genome-wide analyses have identified several single-nucleotide polymorphisms (SNPs) associated with these traits. Univariate methods can identify SNPs associated with behavioral and physiological traits, but multivariate analyses allow identification of clusters of related biologically relevant SNPs and behavioral components. Objectives The aim of the study was to identify clusters of related biologically relevant SNPs and behavioral components in the responses of healthy individuals to d -amphetamine using multivariate analysis. Methods Individuals ( N = 375) without substance abuse histories completed surveys and detailed cardiovascular monitoring during randomized, blinded sessions: d -amphetamine (10 and 20 mg) and placebo. We applied parallel independent component analysis (Para-ICA) to data previously analyzed with univariate approaches, revealing new associations between genes and behavioral responses to d -amphetamine. Results Three significantly associated ( p