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Although prominent personality theories postulate orthogonality between traits of positive emotionality (PEM) and negative emotionality (NEM), empirical evidence often demonstrates the opposite indicating a negative relationship. Therefore, it is not surprising that dopaminergic (DA) gene loci have been related to traits of positive and of NEM. The present genetic association study investigates the influence of two functional DA gene polymorphisms on Sadness as defined by the Affective Neuroscience Personality Scales (ANPS) in healthy Caucasians (n= 1041). We observed a significant interaction effect between the 10‐repeat (10R) allele of the dopamine transporter (DAT1) gene and the methionine (Met) allele of the catechol‐O‐methyltransferase (COMT) Val158Met polymorphism (F_(1,1018)= 11.11; P < 0.001). Carriers of the 9R/9R and the Val/Val genotype showed dramatically reduced Sadness scores in …