APA
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Seidlitz, J., Mallard, T., Vogel, J. W., Lee, Y., Warrier, V., Ball, G., … Alexander-Bloch, A. (2022). The molecular genetic landscape of human brain size variation. BioRxiv.
Chicago/Turabian
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Seidlitz, J., T. Mallard, Jacob W. Vogel, Y. Lee, V. Warrier, Gareth Ball, O. Hansson, et al. “The Molecular Genetic Landscape of Human Brain Size Variation.” bioRxiv (2022).
MLA
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Seidlitz, J., et al. “The Molecular Genetic Landscape of Human Brain Size Variation.” BioRxiv, 2022.
BibTeX Click to copy
@article{j2022a,
title = {The molecular genetic landscape of human brain size variation},
year = {2022},
journal = {bioRxiv},
author = {Seidlitz, J. and Mallard, T. and Vogel, Jacob W. and Lee, Y. and Warrier, V. and Ball, Gareth and Hansson, O. and Hernandez, L. and Mandal, Ayan S. and Wagstyl, K. and Lombardo, M. and Courchesne, E. and Glessner, J. and Satterthwaite, T. and Bethlehem, R. and Bernstock, J. and Tasaki, S. and Ng, B. and Gaiteri, Chris and Smoller, J. and Ge, T. and Gur, R. and Gandal, M. and Alexander-Bloch, A.}
}
Human brain size increases dynamically through early development, peaks in adolescence, and varies up to two-fold among adults. Although previous studies have elucidated changes in brain size across evolution, development, traits, and diseases, the molecular underpinnings of interindividual variation in brain size remain unknown. Here, we leverage postmortem brain RNA sequencing and estimates of brain weight (BW) in 2,531 individuals across three independent datasets, to identify 928 genes that show genome-wide significant associations with either higher or lower BW (BW+, BW-, respectively). These BW gene sets showed distinct neurodevelopmental trajectories and spatial patterns that mapped onto developmental, functional and cellular axes of brain organization. Expression differences among evolutionarily conserved BW genes were predictive of interspecies differences in brain size, and functional annotation of BW genes revealed enrichment for neurogenesis and cell-cell communication. Genome-wide, transcriptome-wide, and phenome-wide association analyses of in vivo neuroimaging phenotypes confirmed that the genetic regulation of BW-transcripts influences cortical surface area and volume, as well as behavioral traits related to brain function and disease. Cumulatively, our study represents a major step towards the goal of delineating the causal mechanisms of human brain size variation in health and disease.