TY - UNPB
T1 - Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
AU - García-Marín, Luis M
AU - Campos, Adrian I
AU - Diaz-Torres, Santiago
AU - Rabinowitz, Jill A
AU - Ceja, Zuriel
AU - Mitchell, Brittany L
AU - Grasby, Katrina L
AU - Thorp, Jackson G
AU - Agartz, Ingrid
AU - Alhusaini, Saud
AU - Ames, David
AU - Amouyel, Philippe
AU - Andreassen, Ole A
AU - Arfanakis, Konstantinos
AU - Vasquez, Alejandro Arias
AU - Armstrong, Nicola J
AU - Athanasiu, Lavinia
AU - Bastin, Mark E
AU - Beiser, Alexa S
AU - Bennett, David A
AU - Bis, Joshua C
AU - Boks, Marco Pm
AU - Boomsma, Dorret I
AU - Brodaty, Henry
AU - Brouwer, Rachel M
AU - Buitelaar, Jan K
AU - Burkhardt, Ralph
AU - Cahn, Wiepke
AU - Calhoun, Vince D
AU - Carmichael, Owen T
AU - Chakravarty, Mallar
AU - Chen, Qiang
AU - Ching, Christopher R K
AU - Cichon, Sven
AU - Crespo-Facorro, Benedicto
AU - Crivello, Fabrice
AU - Dale, Anders M
AU - Smith, George Davey
AU - de Geus, Eco Jc
AU - De Jager, Philip L
AU - de Zubicaray, Greig I
AU - Debette, Stéphanie
AU - DeCarli, Charles
AU - Depondt, Chantal
AU - Desrivières, Sylvane
AU - Ikram, M Kamran
AU - Kahn, Rene S
AU - Klein, Marieke
AU - Shen, Li
AU - Weinberger, Daniel R
PY - 2024/8/15
Y1 - 2024/8/15
N2 - Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, 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 signalling and brain ageing-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 ADHD. 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.
AB - Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, 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 signalling and brain ageing-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 ADHD. 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.
U2 - 10.1101/2024.08.13.24311922
DO - 10.1101/2024.08.13.24311922
M3 - Preprint
C2 - 39371125
T3 - medRxiv
BT - Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
PB - medRxiv
ER -