Left Parietal Functional Connectivity Mediates the Association Between COMT rs4633 and Verbal Intelligence in Healthy Adults.

Qiang Xu,Wen Qin,Tianzi Jiang,Chunshui Yu,Feng Liu,Jilian Fu,Bing Liu

doi:10.3389/fnins.2018.00233

Abstract

In Chinese Han population, Catechol-O-methyltransferase gene (COMT) rs4633 is found to be associated with impaired cognitive process. We aimed to investigate the association between COMT rs4633 and verbal intelligence and the underlying neural mechanisms in Chinese Han healthy young adults. In 256 Chinese Han healthy young adults, we explored the modulatory effects of COMT rs4633 on verbal intelligence quotient (VIQ) and functional connectivity density (FCD) of the brain and the mediation effect of FCD on the association between COMT and VIQ. We further investigated the association between the expression patterns of dopamine receptor genes and the effect of COMT on FCD in the human brain. COMT rs4633 TT homozygotes exhibited lower VIQ than CC homozygotes and TC heterozygotes, higher long-range FCD (lrFCD) than CC homozygotes and TC heterozygotes in the left superior frontal gyrus. TT homozygotes and TC heterozygotes showed higher lrFCD than CC homozygotes in the left inferior parietal lobule. The lrFCD differences across genotypic subgroups were negatively associated with the expression of DRD2 and DRD3 genes. The left parietal lrFCD mediated the association between COMT rs4633 and VIQ. These findings provide a biological pathway that COMT rs4633 affects verbal intelligence via modulating the lrFCD of the left inferior parietal lobule.

Highlights

The central dopaminergic system plays a critical role in human intelligence mainly via coordinating motor activity and influencing on cognitive skills (Guo et al, 2006)
By using Allen Human Brain Atlas (AHBA), we investigated the relationship between expression patterns of two dopamine receptor genes associated with verbal intelligence (Chen et al, 2005; Guo et al, 2006) and statistical map of group differences of functional connectivity density (FCD)
We found no complete linkage disequilibrium (LD) (D′ = 0.8, R2 = 0.56) between Catechol-O-methyltransferase gene (COMT) rs4633 and rs4680 in our Chinese Han population

Summary

Introduction

The central dopaminergic system plays a critical role in human intelligence mainly via coordinating motor activity and influencing on cognitive skills (Guo et al, 2006). COMT activity is regulated by its genetic polymorphism and the COMT gene is one of the most promising candidate genes for human intelligence (Männistö and Kaakkola, 1999; Previc, 1999; Wang et al, 2009; Chen et al, 2016). COMT rs4633 risk T-allele is associated with susceptibility to impaired cognitive process in a Chinese Han population study. It may be induced by increased expression of the COMT gene, which leads to decreased dopamine level, lower functionality in certain brain regions, and bad cognitive performance (Wang et al, 2009).

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