Faculty, Staff and Student Publications
Publication Date
11-1-2024
Journal
Nature Genetics
DOI
10.1038/s41588-024-01951-z
PMID
39433889
PMCID
PMC12088653
PubMedCentral® Posted Date
11-1-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.
Keywords
Humans, Genome-Wide Association Study, Multifactorial Inheritance, Brain, Female, Male, Organ Size, Attention Deficit Disorder with Hyperactivity, Parkinson Disease, Polymorphism, Single Nucleotide, Genomics, Adult, Genetic Predisposition to Disease, Middle Aged, White People
Published Open-Access
yes
Recommended Citation
García-Marín, Luis M; Campos, Adrian I; Diaz-Torres, Santiago; et al., "Genomic Analysis of Intracranial and Subcortical Brain Volumes Yields Polygenic Scores Accounting for Variation Across Ancestries" (2024). Faculty, Staff and Student Publications. 1232.
https://digitalcommons.library.tmc.edu/uthsph_docs/1232