The Impact of Genes and Environment on Brain Ageing in Males Aged 51 to 72 Years

Nathan A. Gillespie*, Sean N. Hatton, Donald J. Hagler, Anders M. Dale, Jeremy A. Elman, Linda K. McEvoy, Lisa T. Eyler, Christine Fennema-Notestine, Mark W. Logue, Ruth E. McKenzie, Olivia K. Puckett, Xin M. Tu, Nathan Whitsel, Hong Xian, Chandra A. Reynolds, Matthew S. Panizzon, Michael J. Lyons, Michael C. Neale, William S. Kremen, Carol Franz

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Magnetic resonance imaging data are being used in statistical models to predicted brain ageing (PBA) and as biomarkers for neurodegenerative diseases such as Alzheimer’s Disease. Despite their increasing application, the genetic and environmental etiology of global PBA indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown. We analyzed data from 734 men from the Vietnam Era Twin Study of Aging with repeated MRI assessments between the ages 51–72 years. Biometrical genetic analyses “twin models” revealed significant and highly correlated estimates of additive genetic heritability ranging from 59 to 75%. Multivariate longitudinal modeling revealed that covariation between PBA at different timepoints could be explained by a single latent factor with 73% heritability. Our results suggest that genetic influences on PBA are detectable in midlife or earlier, are longitudinally very stable, and are largely explained by common genetic influences.

Original languageEnglish
Article number831002
Pages (from-to)1-10
Number of pages10
JournalFrontiers in Aging Neuroscience
Volume14
Issue numberApril
Early online date15 Apr 2022
DOIs
Publication statusPublished - Apr 2022

Bibliographical note

Funding Information:
This work was supported by the National Institute on Aging at the National Institutes of Health grant numbers R01s AG050595, AG022381, AG037985; R25 AG043364, F31 AG064834, P01 AG055367, and AG062483. The funding sources had no role in the preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication.

Funding Information:
We would like to acknowledge the continued cooperation and participation of the members of the VET Registry and their families. The U.S. Department of Veterans Affairs, Department of Defense, National Personnel Records Center, National Archives and Records Administration, Internal Revenue Service, National Opinion Research Center, National Research Council, National Academy of Sciences, and the Institute for Survey Research, Temple University provided invaluable assistance in the conduct of the VET Registry. The Cooperative Studies Program of the U.S. Department of Veterans Affairs provided financial support for development and maintenance of the Vietnam Era Twin Registry.

Publisher Copyright:
Copyright © 2022 Gillespie, Hatton, Hagler, Dale, Elman, McEvoy, Eyler, Fennema-Notestine, Logue, McKenzie, Puckett, Tu, Whitsel, Xian, Reynolds, Panizzon, Lyons, Neale, Kremen and Franz.

Funding

This work was supported by the National Institute on Aging at the National Institutes of Health grant numbers R01s AG050595, AG022381, AG037985; R25 AG043364, F31 AG064834, P01 AG055367, and AG062483. The funding sources had no role in the preparation, review, or approval of the manuscript, or the decision to submit the manuscript for publication. We would like to acknowledge the continued cooperation and participation of the members of the VET Registry and their families. The U.S. Department of Veterans Affairs, Department of Defense, National Personnel Records Center, National Archives and Records Administration, Internal Revenue Service, National Opinion Research Center, National Research Council, National Academy of Sciences, and the Institute for Survey Research, Temple University provided invaluable assistance in the conduct of the VET Registry. The Cooperative Studies Program of the U.S. Department of Veterans Affairs provided financial support for development and maintenance of the Vietnam Era Twin Registry.

FundersFunder number
National Institutes of HealthAG022381, R01s AG050595, AG062483, R25 AG043364, F31 AG064834, P01 AG055367, AG037985
National Institutes of Health
National Institute on Aging
U.S. Department of Veterans Affairs

    Keywords

    • Alzheimers’s disease
    • cognitive decline
    • development
    • gene
    • longitudinal predicted brain aging
    • MRI
    • predicted brain ageing
    • twin

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