Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Luis M García-Marín; Adrian I Campos; Santiago Diaz-Torres; Jill A Rabinowitz; Zuriel Ceja; Brittany L Mitchell; Katrina L Grasby; Jackson G Thorp; Ingrid Agartz; Saud Alhusaini; David Ames; Philippe Amouyel; Ole A Andreassen; Konstantinos Arfanakis; Alejandro Arias-Vasquez; Nicola J Armstrong; Lavinia Athanasiu; Mark E Bastin; Alexa S Beiser; David A Bennett; Joshua C Bis; Marco P M Boks; Dorret I Boomsma; Henry Brodaty; Rachel M Brouwer; Jan K Buitelaar; Ralph Burkhardt; Wiepke Cahn; Vince D Calhoun; Owen T Carmichael; Mallar Chakravarty; Qiang Chen; Christopher R K Ching; Sven Cichon; Benedicto Crespo-Facorro; Fabrice Crivello; Anders M Dale; George Davey Smith; Eco J C de Geus; Philip L De Jager; Greig I de Zubicaray; Stéphanie Debette; Charles DeCarli; Chantal Depondt; Sylvane Desrivières; Srdjan Djurovic; Stefan Ehrlich; Susanne Erk; Thomas Espeseth; Guillén Fernández; Et al.; Dennis van der Meer; Miguel E. Renteria

doi:10.1038/s41588-024-01951-z

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Luis M García-Marín, Adrian I Campos, Santiago Diaz-Torres, Jill A Rabinowitz, Zuriel Ceja, Brittany L Mitchell, Katrina L Grasby, Jackson G Thorp, Ingrid Agartz, Saud Alhusaini, David Ames, Philippe Amouyel, Ole A Andreassen, Konstantinos Arfanakis, Alejandro Arias-Vasquez, Nicola J Armstrong, Lavinia Athanasiu, Mark E Bastin, Alexa S Beiser, David A BennettJoshua C Bis, Marco P M Boks, Dorret I Boomsma, Henry Brodaty, Rachel M Brouwer, Jan K Buitelaar, Ralph Burkhardt, Wiepke Cahn, Vince D Calhoun, Owen T Carmichael, Mallar Chakravarty, Qiang Chen, Christopher R K Ching, Sven Cichon, Benedicto Crespo-Facorro, Fabrice Crivello, Anders M Dale, George Davey Smith, Eco J C de Geus, Philip L De Jager, Greig I de Zubicaray, Stéphanie Debette, Charles DeCarli, Chantal Depondt, Sylvane Desrivières, Srdjan Djurovic, Stefan Ehrlich, Susanne Erk, Thomas Espeseth, Guillén Fernández, Et al., Dennis van der Meer, Miguel E. Renteria^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	2333–2344
Number of pages	12
Journal	Nature Genetics
Volume	56
Issue number	11
DOIs	https://doi.org/10.1038/s41588-024-01951-z
Publication status	Published - 21 Oct 2024

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García-Marín, L. M., Campos, A. I., Diaz-Torres, S., Rabinowitz, J. A., Ceja, Z., Mitchell, B. L., Grasby, K. L., Thorp, J. G., Agartz, I., Alhusaini, S., Ames, D., Amouyel, P., Andreassen, O. A., Arfanakis, K., Arias-Vasquez, A., Armstrong, N. J., Athanasiu, L., Bastin, M. E., Beiser, A. S., ... Renteria, M. E. (2024). Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries. Nature Genetics, 56(11), 2333–2344. https://doi.org/10.1038/s41588-024-01951-z

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title = "Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries",

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.",

author = "Garc{\'i}a-Mar{\'i}n, {Luis M} and Campos, {Adrian I} and Santiago Diaz-Torres and Rabinowitz, {Jill A} and Zuriel Ceja and Mitchell, {Brittany L} and Grasby, {Katrina L} and Thorp, {Jackson G} and Ingrid Agartz and Saud Alhusaini and David Ames and Philippe Amouyel and Andreassen, {Ole A} and Konstantinos Arfanakis and Alejandro Arias-Vasquez and Armstrong, {Nicola J} and Lavinia Athanasiu and Bastin, {Mark E} and Beiser, {Alexa S} and Bennett, {David A} and Bis, {Joshua C} and Boks, {Marco P M} and Boomsma, {Dorret I} and Henry Brodaty and Brouwer, {Rachel M} and Buitelaar, {Jan K} and Ralph Burkhardt and Wiepke Cahn and Calhoun, {Vince D} and Carmichael, {Owen T} and Mallar Chakravarty and Qiang Chen and Ching, {Christopher R K} and Sven Cichon and Benedicto Crespo-Facorro and Fabrice Crivello and Dale, {Anders M} and Smith, {George Davey} and {de Geus}, {Eco J C} and {De Jager}, {Philip L} and {de Zubicaray}, {Greig I} and St{\'e}phanie Debette and Charles DeCarli and Chantal Depondt and Sylvane Desrivi{\`e}res and Srdjan Djurovic and Stefan Ehrlich and Susanne Erk and Thomas Espeseth and Guill{\'e}n Fern{\'a}ndez and {Et al.} and {van der Meer}, Dennis and Renteria, {Miguel E.}",

year = "2024",

month = oct,

day = "21",

doi = "10.1038/s41588-024-01951-z",

language = "English",

volume = "56",

pages = "2333–2344",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

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García-Marín, LM, Campos, AI, Diaz-Torres, S, Rabinowitz, JA, Ceja, Z, Mitchell, BL, Grasby, KL, Thorp, JG, Agartz, I, Alhusaini, S, Ames, D, Amouyel, P, Andreassen, OA, Arfanakis, K, Arias-Vasquez, A, Armstrong, NJ, Athanasiu, L, Bastin, ME, Beiser, AS, Bennett, DA, Bis, JC, Boks, MPM, Boomsma, DI, Brodaty, H, Brouwer, RM, Buitelaar, JK, Burkhardt, R, Cahn, W, Calhoun, VD, Carmichael, OT, Chakravarty, M, Chen, Q, Ching, CRK, Cichon, S, Crespo-Facorro, B, Crivello, F, Dale, AM, Smith, GD, de Geus, EJC, De Jager, PL, de Zubicaray, GI, Debette, S, DeCarli, C, Depondt, C, Desrivières, S, Djurovic, S, Ehrlich, S, Erk, S, Espeseth, T, Fernández, G, Et al., van der Meer, D & Renteria, ME 2024, 'Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries', Nature Genetics, vol. 56, no. 11, pp. 2333–2344. https://doi.org/10.1038/s41588-024-01951-z

TY - JOUR

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 - Arias-Vasquez, Alejandro

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 P M

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 J C

AU - De Jager, Philip L

AU - de Zubicaray, Greig I

AU - Debette, Stéphanie

AU - DeCarli, Charles

AU - Depondt, Chantal

AU - Desrivières, Sylvane

AU - Djurovic, Srdjan

AU - Ehrlich, Stefan

AU - Erk, Susanne

AU - Espeseth, Thomas

AU - Fernández, Guillén

AU - Et al.

AU - van der Meer, Dennis

AU - Renteria, Miguel E.

PY - 2024/10/21

Y1 - 2024/10/21

N2 - 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.

AB - 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.

U2 - 10.1038/s41588-024-01951-z

DO - 10.1038/s41588-024-01951-z

M3 - Article

SN - 1061-4036

VL - 56

SP - 2333

EP - 2344

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Abstract

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