Association of COMT val158met and DRD2 G>T genetic polymorphisms with individual differences in motor learning and performance in female young adults

Abstract

Individuals learn new skills at different rates. Given the involvement of corticostriatal pathways in some types of learning, variations in dopaminergic transmission may contribute to these individual differences. Genetic polymorphisms of the catechol-O-methyltransferase (COMT) enzyme and dopamine receptor D2 (DRD2) genes partially determine cortical and striatal dopamine availability, respectively. Individuals who are homozygous for the COMT methionine (met) allele show reduced cortical COMT enzymatic activity, resulting in increased dopamine levels in the prefrontal cortex as opposed to individuals who are carriers of the valine (val) allele. DRD2 G-allele homozygotes benefit from a higher striatal dopamine level compared with T-allele carriers. We hypothesized that individuals who are homozygous for COMT met and DRD2 G alleles would show higher rates of motor learning. Seventy-two young healthy females (20 ± 1.9 yr) performed a sensorimotor adaptation task and a motor sequence learning task. A nonparametric mixed model ANOVA revealed that the COMT val-val group demonstrated poorer performance in the sequence learning task compared with the met-met group and showed a learning deficit in the visuomotor adaptation task compared with both met-met and val-met groups. The DRD2 TT group showed poorer performance in the sequence learning task compared with the GT group, but there was no difference between DRD2 genotype groups in adaptation rate. Although these results did not entirely come out as one might predict based on the known contribution of corticostriatal pathways to motor sequence learning, they support the role of genetic polymorphisms of COMT val158met (rs4680) and DRD2 G>T (rs 1076560) in explaining individual differences in motor performance and motor learning, dependent on task type.

Interactive effects of age and multi-gene profile on motor learning and sensorimotor adaptation

“…We hypothesized that age-related declines in motor learning and performance would be associated with the presence of fewer “high performance alleles” in our three genes of interest. Given our findings with young adults (Noohi et al, 2014), we also predicted that these associations would vary between motor sequence learning and sensorimotor adaptation for both young and older adults.…”

“…As described in our previous report (Noohi et al, 2014), we collected participants’ saliva samples with Oragene DNA self-collection kits. We identified the single nucleotide polymorphisms (SNPs) of COMT (rs4680), DRD2 (rs1076560), and BDNF (rs6265) genes for the provided DNA samples.…”

“…We have recently reported that COMT val-val and DRD2 TT genotypes were associated with poorer performance in motor sequence learning for young adults (Noohi et al, 2014). We also observed that COMT val-val individuals exhibited slower visuomotor adaptation, however, there was no association of the DRD2 TT polymorphism with visuomotor adaptation.…”

“…Given the evidence that motor sequence learning and sensorimotor adaptation rely on dopaminergic processes (Carbon et al, 2004; Joundi et al, 2012; Marinelli et al, 2009; Noohi et al, 2014; Tremblay et al, 2010), we investigated the association of COMT, DRD2, and BDNF polymorphisms with motor learning and performance in healthy young and older adults. To more robustly explain variations in dopamine modulation that links to an individual's behavior, we employed the polygene approach (David et al, 2013; De Quervain and Papassotiropoulos, 2006; Hamrefors et al, 2010; Lluís-Ganella et al, 2010; Nikolova et al, 2011; Noohi et al, 2014; Papenberg et al, 2013; Pearson-Fuhrhop et al, 2013); that is, we created a count score of the number of purportedly high performance alleles (i.e.…”

“…To more robustly explain variations in dopamine modulation that links to an individual's behavior, we employed the polygene approach (David et al, 2013; De Quervain and Papassotiropoulos, 2006; Hamrefors et al, 2010; Lluís-Ganella et al, 2010; Nikolova et al, 2011; Noohi et al, 2014; Papenberg et al, 2013; Pearson-Fuhrhop et al, 2013); that is, we created a count score of the number of purportedly high performance alleles (i.e. alleles that have been previously linked to better performance in cognitive and motor tasks) that an individual carries across COMT, DRD2, and BDNF.…”