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Research Article

Development and aging of cortical thickness correspond to genetic organization patterns

Anders M. Fjell, Håkon Grydeland, Stine K. Krogsrud, View ORCID ProfileInge Amlien, Darius A. Rohani, Lia Ferschmann, Andreas B. Storsve, Christian K. Tamnes, Roser Sala-Llonch, Paulina Due-Tønnessen, Atle Bjørnerud, Anne Elisabeth Sølsnes, Asta K. Håberg, Jon Skranes, Hauke Bartsch, Chi-Hua Chen, Wesley K. Thompson, Matthew S. Panizzon, William S. Kremen, Anders M. Dale, and Kristine B. Walhovd
  1. aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
  2. bDepartment of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, 0424 Oslo, Norway;
  3. cDepartment of Radiology, Rikshospitalet, Oslo University Hospital, 0424 Oslo, Norway;
  4. dThe Interventional Centre, Rikshospitalet, Oslo University Hospital, 0424 Oslo, Norway;
  5. eDepartment of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, 7491 Trondheim, Norway;
  6. fDepartment of Medical Imaging, St. Olav's Hospital, N-7006 Trondheim, Norway;
  7. gDepartment of Neuroscience, Norwegian University of Science and Technology, 7491 Trondheim, Norway;
  8. hDepartment of Radiology, University of California at San Diego, La Jolla, CA 92093;
  9. iDepartment of Psychiatry, University of California at San Diego, La Jolla, CA 92093;
  10. jCenter of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093;
  11. kCenter for Behavioral Genomics Twin Research Laboratory, University of California at San Diego, La Jolla, CA 92093;
  12. lDepartment of Neurosciences, University of California at San Diego, La Jolla, CA 92093

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PNAS first published November 2, 2015; https://doi.org/10.1073/pnas.1508831112
Anders M. Fjell
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
bDepartment of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, 0424 Oslo, Norway;
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  • For correspondence: andersmf@psykologi.uio.no
Håkon Grydeland
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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Stine K. Krogsrud
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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Inge Amlien
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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  • ORCID record for Inge Amlien
Darius A. Rohani
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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Lia Ferschmann
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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Andreas B. Storsve
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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Christian K. Tamnes
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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Roser Sala-Llonch
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
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Paulina Due-Tønnessen
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
cDepartment of Radiology, Rikshospitalet, Oslo University Hospital, 0424 Oslo, Norway;
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Atle Bjørnerud
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
dThe Interventional Centre, Rikshospitalet, Oslo University Hospital, 0424 Oslo, Norway;
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Anne Elisabeth Sølsnes
eDepartment of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, 7491 Trondheim, Norway;
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Asta K. Håberg
fDepartment of Medical Imaging, St. Olav's Hospital, N-7006 Trondheim, Norway;
gDepartment of Neuroscience, Norwegian University of Science and Technology, 7491 Trondheim, Norway;
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Jon Skranes
eDepartment of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, 7491 Trondheim, Norway;
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Hauke Bartsch
hDepartment of Radiology, University of California at San Diego, La Jolla, CA 92093;
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Chi-Hua Chen
hDepartment of Radiology, University of California at San Diego, La Jolla, CA 92093;
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Wesley K. Thompson
iDepartment of Psychiatry, University of California at San Diego, La Jolla, CA 92093;
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Matthew S. Panizzon
jCenter of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093;
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William S. Kremen
jCenter of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093;
kCenter for Behavioral Genomics Twin Research Laboratory, University of California at San Diego, La Jolla, CA 92093;
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Anders M. Dale
iDepartment of Psychiatry, University of California at San Diego, La Jolla, CA 92093;
lDepartment of Neurosciences, University of California at San Diego, La Jolla, CA 92093
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Kristine B. Walhovd
aResearch Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, 0373 Oslo, Norway;
bDepartment of Physical Medicine and Rehabilitation, Unit of Neuropsychology, Oslo University Hospital, 0424 Oslo, Norway;
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  1. Edited by John D. E. Gabrieli, Massachusetts Institute of Technology, Cambridge, MA, and accepted by the Editorial Board September 29, 2015 (received for review May 5, 2015)

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Significance

Here we show that developmental and adult aging-related changes in cortical thickness follow closely the genetic organization of the cerebral cortex. A total of 1,633 MRI scans from 974 participants from 4.1 to 88.5 y of age were used to measure longitudinal changes in cortical thickness, and the topographic pattern of change was compared with the genetic relationship between cortical subdivisions of maximal shared genetic influence, obtained from an independent sample of 406 middle-aged twins. Cortical changes due to maturation and adult age changes adhered to the genetic organization of the cortex, indicating that individual differences in cortical architecture in middle-aged adults have a neurodevelopmental origin and that genetic factors affect cortical changes through life.

Abstract

There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging.

  • genetic
  • cerebral cortex
  • magnetic resonance imaging
  • aging
  • development

Footnotes

  • ↵1To whom correspondence should be addressed. Email: andersmf{at}psykologi.uio.no.
  • Author contributions: A.M.F. and K.B.W. designed research; A.M.F., H.G., S.K.K., I.A., D.A.R., L.F., A.B.S., C.K.T., R.S.-L., P.D.-T., A.B., A.E.S., A.K.H., J.S., H.B., C.-H.C., W.K.T., M.S.P., W.S.K., A.M.D., and K.B.W. performed research; A.M.F., H.G., R.S.-L., and C.-H.C. analyzed data; and A.M.F. and K.B.W. wrote the paper.

  • Conflict of interest statement: A.M.D. is a founder and holds equity in CorTechs Laboratories and also serves on its Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California at San Diego, in accordance with its conflict of interest policies.

  • This article is a PNAS Direct Submission. J.D.E.G. is a guest editor invited by the Editorial Board.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1508831112/-/DCSupplemental.

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Genetic organization of cortical development
Anders M. Fjell, Håkon Grydeland, Stine K. Krogsrud, Inge Amlien, Darius A. Rohani, Lia Ferschmann, Andreas B. Storsve, Christian K. Tamnes, Roser Sala-Llonch, Paulina Due-Tønnessen, Atle Bjørnerud, Anne Elisabeth Sølsnes, Asta K. Håberg, Jon Skranes, Hauke Bartsch, Chi-Hua Chen, Wesley K. Thompson, Matthew S. Panizzon, William S. Kremen, Anders M. Dale, Kristine B. Walhovd
Proceedings of the National Academy of Sciences Nov 2015, 201508831; DOI: 10.1073/pnas.1508831112

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Genetic organization of cortical development
Anders M. Fjell, Håkon Grydeland, Stine K. Krogsrud, Inge Amlien, Darius A. Rohani, Lia Ferschmann, Andreas B. Storsve, Christian K. Tamnes, Roser Sala-Llonch, Paulina Due-Tønnessen, Atle Bjørnerud, Anne Elisabeth Sølsnes, Asta K. Håberg, Jon Skranes, Hauke Bartsch, Chi-Hua Chen, Wesley K. Thompson, Matthew S. Panizzon, William S. Kremen, Anders M. Dale, Kristine B. Walhovd
Proceedings of the National Academy of Sciences Nov 2015, 201508831; DOI: 10.1073/pnas.1508831112
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