The molecular genetic landscape of human brain size variation

Jakob Seidlitz, Travis T. Mallard, Jacob W. Vogel, Younga H. Lee, Varun Warrier, Gareth Ball, Oskar Hansson, Leanna M. Hernandez, Ayan S. Mandal, Konrad Wagstyl, Michael V. Lombardo, Eric Courchesne, Joseph T. Glessner, Theodore D. Satterthwaite, Richard A.I. Bethlehem, Joshua D. Bernstock, Shinya Tasaki, Bernard Ng, Chris Gaiteri, Jordan W. SmollerTian Ge, Raquel E. Gur, Michael J. Gandal, A. F. Alexander-Bloch, Lifespan Brain Chart Consortium

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Human brain size changes dynamically through early development, peaks in adolescence, and varies up to 2-fold among adults. However, the molecular genetic underpinnings of interindividual variation in brain size remain unknown. Here, we leveraged postmortem brain RNA sequencing and measurements of brain weight (BW) in 2,531 individuals across three independent datasets to identify 928 genome-wide significant associations with BW. Genes associated with higher or lower BW showed distinct neurodevelopmental trajectories and spatial patterns that mapped onto functional and cellular axes of brain organization. Expression of BW genes was predictive of interspecies differences in brain size, and bioinformatic annotation revealed enrichment for neurogenesis and cell-cell communication. Genome-wide, transcriptome-wide, and phenome-wide association analyses linked BW gene sets to neuroimaging measurements of brain size and brain-related clinical traits. Cumulatively, these results represent a major step toward delineating the molecular pathways underlying human brain size variation in health and disease.

Originalspråkengelska
Artikelnummer113439
TidskriftCell Reports
Volym42
Nummer11
DOI
StatusPublished - 2023 nov. 28

Bibliografisk information

Publisher Copyright:
© 2023 The Authors

Ämnesklassifikation (UKÄ)

  • Medicinsk genetik

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