Allele-dosage genetic polymorphisms of cannabinoid receptor 1 predict attention, but not working memory performance in humans

Attention and working memory (WM) are under high genetic regulation. Single nucleotide polymorphisms (SNPs) of the CNR1 gene, that encode for CB1R, have previously been shown to be related with individual differences in attentional control and WM. However, it remains unclear whether there is an allele-dosage or a dominant contribution of polymorphisms of CNR1 affecting attention and WM performance. This study evaluated the associations between attention and WM performance and three SNPs of CNR1: rs1406977, rs2180619, and rs1049353, previously associated with both processes. Healthy volunteers (n = 127) were asked to perform the Attention Network Task (ANT) to evaluate their overall attention and alerting, orienting, and executive systems, and the n-back task for evaluating their WM. All subjects were genotyped using qPCR with TaqMan assays; and dominant and additive models were assessed using the risk alleles of each SNP as the predictor variable. Results showed an individual association of the three SNPs with attention performance, but the composite genotype by the three alleles had the greatest contribution. Moreover, the additive-dosage model showed that for each G-allele added to the genotypic configuration, there was an increase in the percentage of correct responses respect to carriers who have no risk alleles in their genotypic configuration. The number of risk alleles in the genotypic configurations did not predict efficiency in any of the attention systems, nor in WM performance. Our model showed a contribution of three single nucleotide polymorphisms of the CNR1 gene to explain 9% of the variance of attention in an additive manner.