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 language | English |
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Pages (from-to) | 1583-1593 |
Number of pages | 11 |
Journal | Human Brain Mapping |
Volume | 42 |
Issue number | 6 |
DOIs | |
Publication status | Published - 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.
Funders | Funder number |
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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 Foundation | S18‐20 [RLM] |
Stichting Trombosedienst & Artsenlaboratorium Rijnmond | |
National Heart, Lung, and Blood Institute | R01HL105756 |
European Research Council | |
ZonMw | 91211021 |
Erasmus Universiteit Rotterdam | |
Ministerie van Volksgezondheid, Welzijn en Sport | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Horizon 2020 | 678543 |
Keywords
- childhood
- infancy
- MRI
- polygenic scores
- subcortical volume
- ultrasound