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PMID: 24082094 Published · ppublish English Clinical Trial Journal Article Multicenter Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Twin Study

Genetic topography of brain morphology.

Chen CH, Fiecas M, Gutiérrez ED, Panizzon MS, Eyler LT, Vuoksimaa E, Thompson WK, Fennema-Notestine C, Hagler DJ, Jernigan TL, Neale MC, Franz CE, Lyons MJ, Fischl B, Tsuang MT, Dale AM, Kremen WS

Abstract

Animal data show that cortical development is initially patterned by genetic gradients largely along three orthogonal axes. We previously reported differences in genetic influences on cortical surface area along an anterior-posterior axis using neuroimaging data of adult human twins. Here, we demonstrate differences in genetic influences on cortical thickness along a dorsal-ventral axis in the same cohort. The phenomenon of orthogonal gradations in cortical organization evident in different structural and functional properties may originate from genetic gradients. Another emerging theme of cortical patterning is that patterns of genetic influences recapitulate the spatial topography of the cortex within hemispheres. The genetic patterning of both cortical thickness and surface area corresponds to cortical functional specializations. Intriguingly, in contrast to broad similarities in genetic patterning, two sets of analyses distinguish cortical thickness and surface area genetically. First, genetic contributions to cortical thickness and surface area are largely distinct; there is very little genetic correlation (i.e., shared genetic influences) between them. Second, organizing principles among genetically defined regions differ between thickness and surface area. Examining the structure of the genetic similarity matrix among clusters revealed that, whereas surface area clusters showed great genetic proximity with clusters from the same lobe, thickness clusters appear to have close genetic relatedness with clusters that have similar maturational timing. The discrepancies are in line with evidence that the two traits follow different mechanisms in neurodevelopment. Our findings highlight the complexity of genetic influences on cortical morphology and provide a glimpse into emerging principles of genetic organization of the cortex.

Keywords
MRI genetics regionalization
MeSH Terms
Brain Cerebral Cortex/diagnostic imaging Cohort Studies Genetics, Medical Humans Magnetic Resonance Imaging Male Middle Aged Radiography Twins, Dizygotic/genetics Twins, Monozygotic/genetics
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Chen Chi-Hua
Departments of Psychiatry, Cognitive Science, Radiology, and Neurosciences, Center for Behavioral Genomics, and Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093.
Fiecas Mark
Gutiérrez E D
Panizzon Matthew S
Eyler Lisa T
Vuoksimaa Eero
Thompson Wesley K
Fennema-Notestine Christine
Hagler Donald J
Jernigan Terry L
Neale Michael C
Franz Carol E
Lyons Michael J
Fischl Bruce
Tsuang Ming T
Dale Anders M
Kremen William S
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2013-10-15
Epub
2013-00-30
Pages
17089-94
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3801007
Subset
IM
Grants
NIA NIH HHS · R01 AG031224 · United States
NIA NIH HHS · R01 AG022982 · United States
NIA NIH HHS · R01 AG018386 · United States
NINDS NIH HHS · NS056883 · United States
NIA NIH HHS · R01 AG018384 · United States
NIDA NIH HHS · DA029475 · United States
NINDS NIH HHS · U54 NS056883 · United States
NIA NIH HHS · AG022381 · United States
NIA NIH HHS · AG018384 · United States
NIA NIH HHS · AG031224 · United States
NIA NIH HHS · AG022982 · United States
NIA NIH HHS · AG018386 · United States
NIDA NIH HHS · RC2 DA029475 · United States
NIA NIH HHS · R01 AG022381 · United States
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