Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries.
Langue
EN
Article de revue
Ce document a été publié dans
Nature Genetics. 2024-11-01, vol. 56, n° 11, p. 2333-2344
Résumé en anglais
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, ...Lire la suite >
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.< Réduire
Mots clés en anglais
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