title: Modulative effects of COMT haplotype on age-related associations with brain morphology.
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.
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, Singapore, 117576, Singapore.
authors.forename: Annie
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, Singapore, 117576, Singapore.|Clinical Imaging Research Center, National University of Singapore, Singapore, 117456, Singapore.|Singapore Institute for Clinical Sciences, the Agency for Science, Technology and Research, Singapore, 117609, Singapore.
authors.forename: Anqi
authors.initials: A
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D060005:Genotyping Techniques; D006239:Haplotypes; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis; D055815:Young Adult
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: aging; cortical thickness; diffeomorphic mapping; genetic variant; haplotype; subcortical shape