Impact of interacting functional variants in COMT on regional gray matter volume in human brain
Open accessAbstract
Background 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.Methods 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.Results 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.Conclusions 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.
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Structural imaging studies report less consistent results on COMT genotype effects.
“Structural imaging studies report less consistent results (14-16).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [16]
Our findings of rs4680 effects on GM volumes are consistent with previous evidence for an effect of this polymorphism on both adolescent and adult GM volumes and cortical thickness.
“Our findings of rs4680 effects on GM volumes are consistent with previous evidence for an effect of this polymorphism on both adolescent and adult GM volumes (14,16) and cortical thickness (15,18).”
From Influence of the COMT genotype on working memory and brain activity changes during development (2011) · cites this paper as [16]
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- Authors
- Honea, R., Verchinski, B. A., Pezawas, L., Kolachana, B. S., Callicott, J. H., Mattay, V. S., Weinberger, D. R., & Meyer-Lindenberg, A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Weinberger, Daniel R.
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 45
- Issue
- 1
- Pages
- 44-51
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2702693
- OpenAlex
- W1970806500
- Cited by
- 128
- References
- 78
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- 6.05
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- journal article
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- en
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- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism
- National Institute of Mental Health (Z01MH002734)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- catechol-O-methyltransferase, COMT gene, COMT Val158Met polymorphism, gene-gene interaction, haplotypes, gray matter volume, hippocampus, dorsolateral prefrontal cortex, dopamine, schizophrenia genetics, brain structure
- MeSH terms
- Adult, Catechol O-Methyltransferase, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurons, Statistics as Topic, Genetic Variation, Prefrontal Cortex, Polymorphism, Single Nucleotide, Imaging, Three-Dimensional
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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