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Heritable changes in regional cortical thickness with age

  • SI: Genetic Neuroimaging in Aging and Age-Related Disease
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Abstract

It is now well established that regional indices of brain structure such as cortical thickness, surface area or grey matter volume exhibit spatially variable patterns of heritability. However, a recent study found these patterns to change with age during development, a result supported by gene expression studies. Changes in heritability have not been investigated in adulthood so far and could have important implications in the study of heritability and genetic correlations in the brain as well as in the discovery of specific genes explaining them. Herein, we tested for genotype by age (G ×A) interactions, an extension of genotype by environment interactions, through adulthood and healthy aging in 902 subjects from the Genetics of Brain Structure (GOBS) study. A “jackknife” based method for the analysis of stable cortical thickness clusters (JASC) and scale selection is also introduced. Although additive genetic variance remained constant throughout adulthood, we found evidence for incomplete pleiotropy across age in the cortical thickness of paralimbic and parieto-temporal areas. This suggests that different genetic factors account for cortical thickness heritability at different ages in these regions.

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Acknowledgments

Financial support for this study was provided by the National Institute of Mental Health grants MH0708143 (Principal Investigator [PI]: DCG), MH078111 (PI: JB), and MH083824 (PI: DCG & JB), Canadian Institutes of Health Research (CIHR) operating grant MOP 37754 (PI: ACE) and by the Natural Sciences and Engineering Research Council of Canada grant # 436141 (PI: PB). Theoretical development of the GxA model and its implementation in SOLAR is supported by National Institute of Mental Health Grant MH59490 (PI: JB). PB is supported by a salary award of the Fonds de recherche du Québec - Santé (FRQS). Authors declare no competing financial interests in relation to the described work.

Conflict of interest

Francois Chouinard-Decorte, D. Reese McKay, Andrew Reid, Budhachandra Khundrakpam, Lu Zhao, Sherif Karama, Pierre Rioux, Emma Sprooten, Emma Knowles, Jack W. Kent, Jr., Joanne E. Curran, Harald H. H. Göring, Thomas D. Dyer, Rene L. Olvera, Peter Kochunov, Ravi Duggirala, Peter T. Fox, Laura Almasy, John Blangero, Pierre Bellec, Alan C. Evans, and David C. Glahn declare that they have no conflicts of interest.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada

    Francois Chouinard-Decorte, Andrew Reid, Budhachandra Khundrakpam, Lu Zhao, Sherif Karama, Pierre Rioux, Rene L. Olvera & Alan C. Evans

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06571, USA

    D. Reese McKay, Emma Sprooten, Emma Knowles, Rene L. Olvera & David C. Glahn

  3. Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT, 06106, USA

    D. Reese McKay, Emma Sprooten, Emma Knowles, Rene L. Olvera & David C. Glahn

  4. Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, QC, H4H 1R2, Canada

    Sherif Karama & Rene L. Olvera

  5. Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, 78245, USA

    Jack W. Kent Jr., Joanne E. Curran, Harald H. H. Göring, Thomas D. Dyer, Rene L. Olvera, Ravi Duggirala, Laura Almasy & John Blangero

  6. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 2120, USA

    Rene L. Olvera & Peter Kochunov

  7. Research Imaging Institute, University of Texas Health Science Center San Antonio, 8403 Floyd Curl Dr, San Antonio, TX, 78229, USA

    Rene L. Olvera & Peter T. Fox

  8. Geriatric Institute Research Center, Université de Montréal, Montréal, QC, H3W 1W5, Canada

    Rene L. Olvera & Pierre Bellec

  9. Department of Psychiatry, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, H3W 1W5, USA

    Rene L. Olvera

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  1. Francois Chouinard-Decorte
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  2. D. Reese McKay
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  3. Andrew Reid
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  4. Budhachandra Khundrakpam
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  5. Lu Zhao
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  6. Sherif Karama
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  7. Pierre Rioux
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  8. Emma Sprooten
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  9. Emma Knowles
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  14. Rene L. Olvera
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  15. Peter Kochunov
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  16. Ravi Duggirala
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  17. Peter T. Fox
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  18. Laura Almasy
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  19. John Blangero
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  20. Pierre Bellec
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  21. Alan C. Evans
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  22. David C. Glahn
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Corresponding author

Correspondence to David C. Glahn.

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Chouinard-Decorte, F., McKay, D.R., Reid, A. et al. Heritable changes in regional cortical thickness with age. Brain Imaging and Behavior 8, 208–216 (2014). https://doi.org/10.1007/s11682-014-9296-x

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