Abstract
Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8–89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
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Data availability
Data availability notes for each cohort can be found on Supplementary Table S1.
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All scripts are available upon reasonable request to the corresponding authors.
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Acknowledgements
This work was funded by the South-Eastern Norway Regional Health Authority (2014097, 2015073, 2016083, and 2019101), the Research Council of Norway (204966, 249795, and 223273), Stiftelsen Kristian Gerhard Jebsen, and the European Research Council under the European Union’s Horizon 2020 research and Innovation program (ERC StG, Grant 802998). Research conducted using the UK Biobank Resource (access code 27412).
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Conceptualization, ACP and LTW; Methodology, ACP and LTW; Investigation, ACP, vdM, and TK; Writing—Original Draft, ACP and LTW; Writing—Review and Editing, all co-authors.
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Córdova-Palomera, A., van der Meer, D., Kaufmann, T. et al. Genetic control of variability in subcortical and intracranial volumes. Mol Psychiatry 26, 3876–3883 (2021). https://doi.org/10.1038/s41380-020-0664-1
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DOI: https://doi.org/10.1038/s41380-020-0664-1
