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The genetic etiology of longitudinal measures of predicted brain ageing in a population-based sample of mid to late-age males

By Nathan A Gillespie, Sean N Hatton, Donald H Hagler, Anders M. Dale, Jeremy A Elman, Linda K. McEvoy, Lisa T Elyer, 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 E Franz

Posted 06 Aug 2021
bioRxiv DOI: 10.1101/2021.08.04.455143

Despite their increasing application, the genetic and environmental etiology of global predicted brain ageing (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 52 to 72 years. Biometrical genetic analyses revealed significant and highly correlated estimates of additive genetic heritability ranging from 59% to 75%. Multivariate longitudinal modelling 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.

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