Distinct Genetic Influences on Cortical Surface Area and Cortical Thickness
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Neuroimaging studies examining the effects of aging and neuropsychiatric disorders on the cerebral cortex have largely been based on measures of cortical volume. Given that cortical volume is a product of thickness and surface area, it is plausible that measures of volume capture at least 2 distinct sets of genetic influences. The present study aims to examine the genetic relationships between measures of cortical surface area and thickness. Participants were men in the Vietnam Era Twin Study of Aging (110 monozygotic pairs and 92 dizygotic pairs). Mean age was 55.8 years (range: 51-59). Bivariate twin analyses were utilized in order to estimate the heritability of cortical surface area and thickness, as well as their degree of genetic overlap. Total cortical surface area and average cortical thickness were both highly heritable (0.89 and 0.81, respectively) but were essentially unrelated genetically (genetic correlation = 0.08). This pattern was similar at the lobar and regional levels of analysis. These results demonstrate that cortical volume measures combine at least 2 distinct sources of genetic influences. We conclude that using volume in a genetically informative study, or as an endophenotype for a disorder, may confound the underlying genetic architecture of brain structure.
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Cellular mechanisms and heritability underlying SA expansion are thought to differ from mechanisms underlying cortical thickness.
“Cellular mechanisms and heritability underlying SA expansion are thought to differ from mechanisms underlying cortical thickness 17,18 , and SA hyper-expansion has been reported in genetically-engineered mouse models of autism 19 .”
From Early brain development in infants at high risk for autism spectrum disorder (2017) · cites this paper as [17]
Area and thickness are genetically unrelated but often confounded in measures of cortical volume.
“Area and thickness are genetically unrelated (39) but often confounded in measures of cortical volume, which is the product of the two.”
From Multimodal imaging of the self-regulating developing brain (2012) · cites this paper as [39]
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“cortical shape)(238,239) – and that different morphological features may have different neuropathological and genetic underpinnings.(240) So far, individual aspects of the cortex are generally explored in isolation (i.”
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- Authors
- Panizzon, M. S., Fennema-Notestine, C., Eyler, L. T., Jernigan, T. L., Prom-Wormley, E., Neale, M., Jacobson, K., Lyons, M. J., Grant, M. D., Franz, C. E., Xian, H., Tsuang, M., Fischl, B., Seidman, L., Dale, A., & Kremen, W. S.
- Affiliations
- University of California San Diego (US)
- VA San Diego Healthcare System (US)
- Virginia Commonwealth University (US)
- University of Chicago (US)
- Boston University (US)
- Washington University in St. Louis (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-03-18
- Volume
- 19
- Issue
- 11
- Pages
- 2728-2735
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- PMC
- PMC2758684
- OpenAlex
- W2111884236
- Cited by
- 1,304
- References
- 54
- Citations by year
- 2026: 71 · 2025: 65 · 2024: 68 · 2023: 99 · 2022: 78 · 2021: 113 · 2020: 101 · 2019: 100 · 2018: 97 · 2017: 78 · 2016: 88 · 2015: 85 · 2014: 69 · 2013: 59 · 2012: 54
- FWCI
- 25.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Defense
- U.S. Department of Veterans Affairs (U24 RR021382)
- Temple University
- National Institutes of Health (R01 AG18386)
- National Institute on Aging (R01AG22381, R01 AG18386, R01AG022982, R01 AG18384, R01AG022381, R01AG018384, R01AG-22982, R01AG018386)
- National Center for Research Resources (U24RR021382)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- cortical surface area, cortical thickness, heritability, genetic correlation, cortical volume, endophenotypes, twin studies, aging
- MeSH terms
- Cerebral Cortex, Humans, Male, Middle Aged, Organ Size, Twins
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.
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