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

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