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. 2016 Jun;37(6):2068-82.
doi: 10.1002/hbm.23161. Epub 2016 Feb 27.

Modulative effects of COMT haplotype on age-related associations with brain morphology

Annie Lee  1 , Anqi Qiu  1   2   3
Affiliations

Modulative effects of COMT haplotype on age-related associations with brain morphology

Annie Lee et al. Hum Brain Mapp. 2016 Jun.

Abstract

Catechol-O-methyltransferase (COMT), located on chromosome 22q11.2, encodes an enzyme critical for dopamine flux in the prefrontal cortex. Genetic variants of COMT have been suggested to functionally manipulate prefrontal morphology and function in healthy adults. This study aims to investigate modulative roles of individuals COMT SNPs (rs737865, val158met, rs165599) and its haplotypes in age-related brain morphology using an Asian sample with 174 adults aged from 21 to 80 years. We showed an age-related decline in cortical thickness of the dorsal visual pathway, including the left dorsolateral prefrontal cortex, bilateral angular gyrus, right superior frontal cortex, and age-related shape compression in the basal ganglia as a function of the genotypes of the individual COMT SNPs, especially COMT val158met. Using haplotype trend regression analysis, COMT haplotype probabilities were estimated and further revealed an age-related decline in cortical thickness in the default mode network (DMN), including the posterior cingulate, precuneus, supramarginal and paracentral cortex, and the ventral visual system, including the occipital cortex and left inferior temporal cortex, as a function of the COMT haplotype. Our results provided new evidence on an antagonistic pleiotropic effect in COMT, suggesting that genetically programmed neural benefits in early life may have a potential bearing towards neural susceptibility in later life. Hum Brain Mapp 37:2068-2082, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: aging; cortical thickness; diffeomorphic mapping; genetic variant; haplotype; subcortical shape.

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Figures

Figure 1
Figure 1
Panels (A) and (D) show the statistical maps of interaction between age and COMT SNPs (val158met, rs737865) on cortical thickness. Scatter plots on panels (B) and (E) illustrate the relationship of age and cortical thickness within each genotype of COMT val158met and COMT rs737865, respectively. Boxplots on panels (C) and (F) illustrate the cortical thickness within genotypes of COMT val158met and rs737865 in each age groups, respectively. Abbreviation: *P < 0.05. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]
Figure 2
Figure 2
Panels (A) shows the statistical maps of interaction between age and COMT SNPs (val158met, rs737865) on subcortical shapes. The scatter plots on panel (B) illustrate the relationship of age and subcortical shapes within each genotype of COMT val4680met. The boxplot on panel (C) illustrates the subcortical shapes between genotypes of COMT val4680met in each age group. Abbreviation: *P < 0.05. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]
Figure 3
Figure 3
Panels (A) and (B) illustrate statistical maps for the relationship between cortical thickness and age modulated by G‐met‐A haplotype probability and G‐val‐A haplotype probability. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]
Figure 4
Figure 4
Panels (A, B and C) illustrate statistical maps for the relationship between subcortical shape and age modulated by A‐met‐A haplotype probability, G‐met‐A haplotype probability and A‐val‐G haplotype probability. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]
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