Title
Impact of interacting functional variants in COMT on regional gray matter volume in human brain.
Abstract
Functional variants in the catechol-O-methyltransferase (COMT) gene have been shown to impact cognitive function, cortical physiology and risk for schizophrenia. A recent study showed that previously reported effects of the functional val158met SNP (rs4680) on brain function are modified by other functional SNPs and haplotypes in the gene, though it was unknown if these effects are also seen in brain structure.We used voxel-based morphometry to investigate the impact of multiple functional variants in COMT on gray matter volume in a large group of 151 healthy volunteers from the CBDB/NIMH Genetic Study of Schizophrenia.We found that the previously described rs4680 val risk variant affects hippocampal and dorsolateral prefrontal (DLPFC) gray matter volume. In addition, we found that this SNP interacts with a variant in the P2 promoter region (rs2097603) in predicting changes in hippocampal gray matter volume consistent with a nonlinear effect of extracellular dopamine.We report evidence that interacting functional variants in COMT affect gray matter regional volume in hippocampus and DLPFC, providing further in vivo validation of the biological impact of complex genetic variation in COMT on neural systems relevant for the pathophysiology of schizophrenia and extending observations of nonlinear dependence of prefrontal neurons on extracellular dopamine to the domain of human brain structure.
Year
DOI
Venue
2009
10.1016/j.neuroimage.2008.10.064
NeuroImage
Keywords
Field
DocType
cognitive function,genetic variation,magnetic resonance imaging,hippocampus,catechol o methyltransferase
Developmental psychology,Catechol-O-methyl transferase,Neuroscience,Prefrontal cortex,Psychology,Dopamine,Human brain,Hippocampal formation,Hippocampus,Schizophrenia,rs4680
Journal
Volume
Issue
ISSN
45
1
1053-8119
Citations 
PageRank 
References 
7
1.02
5
Authors
8