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Impact of five SNP s in dopamine‐related genes on executive function
Author(s) -
Mitaki S.,
Isomura M.,
Maniwa K.,
Yamasaki M.,
Nagai A.,
Nabika T.,
Yamaguchi S.
Publication year - 2013
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.2012.01673.x
Subject(s) - rs4680 , single nucleotide polymorphism , population , snp , multifactor dimensionality reduction , dopamine , catechol o methyl transferase , genetics , medicine , allele , psychology , biology , gene , genotype , environmental health
Objectives Dopamine neurotransmission is a critical factor for executive function, which is controlled by the prefrontal cortex in humans. Although the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged, identification of a genotype–phenotype association has not yet been clearly established. In this study, we therefore evaluated the effects of five functional single‐nucleotide polymorphisms ( SNP s) in specific genes related to dopamine neurotransmission on executive function in a general population. Materials and methods Participants of the health examination at the Shimane Institute of Health Science were recruited for this study ( n = 964). To evaluate executive function, the F rontal A ssessment B attery ( FAB ) was administered. SNP s were genotyped using the T aq M an method. Results A significant association was found between an SNP in the catechol‐ O ‐methyltransferase ( COMT ) gene (rs4680) encoding the low‐activity M et allele and FAB score ( P = 0.003). Of note, the flexibility subset of the FAB was associated with the SNP in COMT ( P = 0.003) after adjustment for confounding factors. The generalized multifactor dimensionality reduction method identified that the combination of two SNP s in the COMT gene (rs4680) and the dopamine D 4 receptor gene (rs1800955) had a significant effect on FAB score. Conclusions Our study indicates a contribution of rs4680 in the COMT gene to the variability in executive function, as assessed by the FAB . In addition, we have indicated that a complex gene–gene interaction between SNP s in the genes related to dopamine neurotransmission may influence executive function in a general population.