Abstract
DOPA decarboxylase (DDC) is involved in the synthesis of dopamine, norepinephrine and serotonin. It has been suggested that genes involved in the dopamine, norepinephrine, and cholinergic systems play an essential role in the efficiency of human attention networks. Attention refers to the cognitive process of obtaining and maintaining the alert state, orienting to sensory events, and regulating the conflicts of thoughts and behavior. The present study tested seven single nucleotide polymorphisms (SNPs) within the DDC gene for association with attention, which was assessed by the Attention Network Test to detect three networks of attention, including alerting, orienting, and executive attention, in a healthy Han Chinese sample (N=451). Association analysis for individual SNPs indicated that four of the seven SNPs (rs3887825, rs7786398, rs10499695, and rs6969081) were significantly associated with alerting attention. Haplotype-based association analysis revealed that alerting was associated with the haplotype G-A-T for SNPs rs7786398-rs10499695-rs6969081. These associations remained significant after correcting for multiple testing by max(T) permutation. No association was found for orienting and executive attention. This study provides the first evidence for the involvement of the DDC gene in alerting attention. A better understanding of the genetic basis of distinct attention networks would allow us to develop more effective diagnosis, treatment, and prevention of deficient or underdeveloped alerting attention as well as its related prevalent neuropsychiatric disorders.
Highlights
Attention is a central cognitive process involved in selectively concentrating on a certain aspect of the environment
All significant associations were corrected for multiple testing by the max(T) permutations permutation approach in Plink (10000 permutation) for individual single nucleotide polymorphisms (SNPs) analysis and haplotype-based association analysis considering all tests done for all three traits
The same four SNPs in the DOPA decarboxylase (DDC) gene were still significantly associated with alerting attention after controlling for the covariate
Summary
Attention is a central cognitive process involved in selectively concentrating on a certain aspect of the environment. Several previous studies detected associations between various genes with relevance for neurotransmission and specific attention networks using the ANT. A genome-wide association study supported the association between the DDC gene and inattentive ADHD using over 900 ADHD Caucasian probandparent trios (i.e., International Multicenter ADHD Genetics [IMAGE] project dataset) (Lasky-Su et al, 2008). This association was confirmed in a Chinese Han sample (Guan et al, 2009). The DDC gene is involved with three important neurotransmitter systems (i.e., dopamine, norepinephrine, and serotonin), and these neurotransmitters are related to the attention networks. We analyzed seven SNPs selected to cover the whole DDC gene to explore whether there exists an association of the DDC gene with specific attention network inefficiency
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