Open AccessModulative effects of COMT haplotype on age‐related associations with brain morphology
Author(s) -
Lee Annie,
Qiu Anqi
Publication year - 2016
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.23161
Subject(s) - precuneus , catechol o methyl transferase , posterior cingulate , anterior cingulate cortex , neuroscience , prefrontal cortex , haplotype , premotor cortex , psychology , brain morphometry , occipital lobe , single nucleotide polymorphism , default mode network , cortex (anatomy) , dorsolateral prefrontal cortex , cingulate cortex , medial frontal gyrus , biology , functional magnetic resonance imaging , allele , genetics , genotype , anatomy , medicine , central nervous system , dorsum , magnetic resonance imaging , cognition , radiology , gene
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.