Genetic scores for adult subcortical volumes associate with subcortical volumes during infancy and childhood

Sander Lamballais, Philip R. Jansen, Jeremy A. Labrecque, M. Arfan Ikram, Tonya White*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Individual differences in subcortical brain volumes are highly heritable. Previous studies have identified genetic variants that underlie variation in subcortical volumes in adults. We tested whether those previously identified variants also affect subcortical regions during infancy and early childhood. The study was performed within the Generation R study, a prospective birth cohort. We calculated polygenic scores based on reported GWAS for volumes of the accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus. Participants underwent cranial ultrasound around 7 weeks of age (range: 3–20), and we obtained metrics for the gangliothalamic ovoid, a predecessor of the basal ganglia. Furthermore, the children participated in a magnetic resonance imaging (MRI) study around the age of 10 years (range: 9–12). A total of 340 children had complete data at both examinations. Polygenic scores primarily associated with their corresponding volumes at 10 years of age. The scores also moderately related to the diameter of the gangliothalamic ovoid on cranial ultrasound. Mediation analysis showed that the genetic influence on subcortical volumes at 10 years was only mediated for 16.5–17.6% of the total effect through the gangliothalamic ovoid diameter at 7 weeks of age. Combined, these findings suggest that previously identified genetic variants in adults are relevant for subcortical volumes during early life, and that they affect both prenatal and postnatal development of the subcortical regions.

Original languageEnglish
Pages (from-to)1583-1593
Number of pages11
JournalHuman Brain Mapping
Volume42
Issue number6
DOIs
Publication statusPublished - 15 Apr 2021

Bibliographical note

Funding Information:
The work was supported by ZonMw (TOP project 91211021 [Tonya White]), the Sophia Foundation (grant S18‐20 [RLM]) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project: ORACLE, grant agreement No: 678543 [Sander Lamballais, M. Arfan Ikram]). The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR‐MDC), Rotterdam. The authors gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families.

Funding Information:
The work was supported by ZonMw (TOP project 91211021 [Tonya White]), the Sophia Foundation (grant S18-20 [RLM]) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project: ORACLE, grant agreement No: 678543 [Sander Lamballais, M. Arfan Ikram]). The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The authors gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families.

Publisher Copyright:
© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

The work was supported by ZonMw (TOP project 91211021 [Tonya White]), the Sophia Foundation (grant S18‐20 [RLM]) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project: ORACLE, grant agreement No: 678543 [Sander Lamballais, M. Arfan Ikram]). The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR‐MDC), Rotterdam. The authors gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families. The work was supported by ZonMw (TOP project 91211021 [Tonya White]), the Sophia Foundation (grant S18-20 [RLM]) and the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (project: ORACLE, grant agreement No: 678543 [Sander Lamballais, M. Arfan Ikram]). The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. The authors gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organization for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families.

FundersFunder number
Erasmus Medical Center, Rotterdam
Ministry of Youth and Families
Municipal Health Service Rotterdam
Netherlands Organization for Health Research and Development
Rotterdam Homecare Foundation
STAR-MDC
Sophia FoundationS18‐20 [RLM]
Stichting Trombosedienst & Artsenlaboratorium Rijnmond
National Heart, Lung, and Blood InstituteR01HL105756
European Research Council
ZonMw91211021
Erasmus Universiteit Rotterdam
Ministerie van Volksgezondheid, Welzijn en Sport
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Horizon 2020678543

    Keywords

    • childhood
    • infancy
    • MRI
    • polygenic scores
    • subcortical volume
    • ultrasound

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