Brain morphology, autistic traits, and polygenic risk for autism: A population-based neuroimaging study

Silvia Alemany*, Elisabet Blok, Philip R. Jansen, Ryan L. Muetzel, Tonya White

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Autism spectrum disorders (ASD) are associated with widespread brain alterations. Previous research in our group linked autistic traits with altered gyrification, but without pronounced differences in cortical thickness. Herein, we aim to replicate and extend these findings using a larger and older sample. Additionally, we examined whether (a) brain correlates of autistic traits were associated with polygenic risk scores (PRS) for ASD, and (b) autistic traits are related with brain morphological changes over time in a subset of children with longitudinal data available. The sample included 2400 children from the Generation R cohort. Autistic traits were measured using the Social Responsiveness Scale (SRS) at age 6 years. Gyrification, cortical thickness, surface area, and global morphological measures were obtained from high-resolution structural MRI scans at ages 9-to-12 years. We performed multiple linear regression analyses on a vertex-wise level. Corresponding regions of interest were tested for association with PRS. Results showed that autistic traits were related to (a) lower gyrification in the lateral occipital and the superior and inferior parietal lobes, (b) lower cortical thickness in the superior frontal region, and (c) lower surface area in inferior temporal and rostral middle frontal regions. PRS for ASD and longitudinal analyses showed significant associations that did not survive correction for multiple testing. Our findings support stability in the relationship between higher autistic symptoms and lower gyrification and smaller surface areas in school-aged children. These relationships remained when excluding ASD cases, providing neurobiological evidence for the extension of autistic traits into the general population. Lay Summary: We found that school-aged children with higher levels of autistic traits had smaller total brain volume, cerebellum, cortical thickness, and surface area. Further, we also found differences in the folding patterns of the brain (gyrification). Overall, genetic susceptibility for autism spectrum disorders was not related to these brain regions suggesting that other factors could be involved in their origin. These results remained significant when excluding children with a diagnosis of ASD, providing support for the extension of the relationship between autistic traits and brain findings into the general population.

Original languageEnglish
Pages (from-to)2085-2099
Number of pages15
JournalAutism Research
Volume14
Issue number10
Early online date26 Jul 2021
DOIs
Publication statusPublished - Oct 2021

Bibliographical note

Funding Information:
The authors thank the participants and their parents that contributed to the Generation R Study, and the researchers who were involved in data collection. This work was supported by the Sophia Foundation for Scientific Research (SSWO project number: S14‐27, S18‐68, and S20‐48) and the Netherlands Organization for Health Research and Development (ZonMw) TOP project number 91211021 to T. White. R. Muetzel was supported by the Sophia Foundation (S18‐20) and the Erasmus University Fellowship. Supercomputing computations were supported by the NWO Physical Sciences Division (Exacte Wetenschappen) and SURFsara (Cartesius computer cluster, www.surfsara.nl ). 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 (STARMDC). SA is funded by a Juan de la Cierva—Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry, and Competitiveness (IJCI‐2017‐34068). ISGlobal acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018‐000806‐S), and support from the Generalitat de Catalunya through the CERCA Program.

Funding Information:
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 (STARMDC); Juan de la Cierva ‐ Incorporación Postdoctoral Contract awarded by Ministry of Economy, Industry and Competitiveness, Grant/Award Number: IJCI‐2017‐34068; Netherlands Organization for Health Research and Development (ZonMw), Grant/Award Number: 91211021; NWO Physical Sciences Division (Exacte Wetenschappen) and SURFsara (Cartesius computer cluster, www.surfsara.nl); Sophia Foundation (S18‐20) and the Erasmus University Fellowship, Grant/Award Number: S18‐20; Sophia Foundation for Scientific Research (SSWO), Grant/Award Numbers: S14‐27, S18‐68, S20‐48 Funding information

Funding Information:
The authors thank the participants and their parents that contributed to the Generation R Study, and the researchers who were involved in data collection. This work was supported by the Sophia Foundation for Scientific Research (SSWO project number: S14-27, S18-68, and S20-48) and the Netherlands Organization for Health Research and Development (ZonMw) TOP project number 91211021 to T. White. R. Muetzel was supported by the Sophia Foundation (S18-20) and the Erasmus University Fellowship. Supercomputing computations were supported by the NWO Physical Sciences Division (Exacte Wetenschappen) and SURFsara (Cartesius computer cluster, www.surfsara.nl). 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 (STARMDC). SA is funded by a Juan de la Cierva?Incorporaci?n Postdoctoral Contract awarded by Ministry of Economy, Industry, and Competitiveness (IJCI-2017-34068). ISGlobal acknowledge support from the Spanish Ministry of Science and Innovation through the ?Centro de Excelencia Severo Ochoa 2019?2023? Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.

Publisher Copyright:
© 2021 International Society for Autism Research, Wiley Periodicals LLC.

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

Keywords

  • autism
  • cortical thickness
  • genetics
  • gyrification
  • surface area

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