Polygenic Risk Scores for Developmental Disorders, Neuromotor Functioning During Infancy, and Autistic Traits in Childhood

Fadila Serdarevic, Henning Tiemeier*, Philip R. Jansen, Silvia Alemany, Yllza Xerxa, Alexander Neumann, Elise Robinson, Manon H.J. Hillegers, Frank C. Verhulst, Akhgar Ghassabian

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

23 Downloads (Pure)

Abstract

Background: Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. 

Methods: In a population-based cohort in The Netherlands (2002–2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9–20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. 

Results: Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism–based heritability of overall motor development was 20% (SE =.21) and of autistic traits was 68% (SE =.26). The genetic correlation between overall motor development and autistic traits was.35 (SE =.21, p <.001). 

Conclusions: We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.

Original languageEnglish
Pages (from-to)132-138
Number of pages7
JournalBiological Psychiatry
Volume87
Issue number2
Early online date18 Jun 2019
DOIs
Publication statusPublished - 15 Jan 2020

Funding

The general design of the Generation R Study is supported by the Erasmus Medical Center Rotterdam, the Erasmus University Rotterdam , the Netherlands Organization for Health Research and Development (ZonMw “Geestkracht” programme 10.000.1003), the Netherlands Organization for Scientific Research (NOW), and the Ministry of Health, Welfare and Sport . The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and the Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, the Rotterdam Homecare Foundation, and the Stichting Trombosedienst en Artsenlaboratorium Rijnmond. HT was supported by a grant of the Dutch Ministry of Education, Culture, and Science and the NWO (Grant No. 024.001.003 , Consortium on Individual Development). A Ter Meulen grant financed by the Dutch Government and an Erasmus Mundus–Western Balkans (ERAWEB) scholarship grant financed by the European Commission were awarded to FS (Grant No. 2013-2548/001-001-EMA2 ). The authors report no biomedical financial interests or potential conflicts of interest.

FundersFunder number
Dutch Government
Dutch Ministry of Education, Culture, and Science
Erasmus Medical Center Rotterdam
Municipal Health Service Rotterdam
Rotterdam Homecare Foundation
Stichting Trombosedienst en Artsenlaboratorium Rijnmond
ZonMw10.000.1003
Erasmus Universiteit Rotterdam
Ministerie van Volksgezondheid, Welzijn en Sport
Nederlandse Organisatie voor Wetenschappelijk Onderzoek024.001.003
Erasmus+2013-2548/001-001-EMA2

    Keywords

    • ADHD
    • Autism
    • Cohort
    • Infant
    • Neuromotor
    • Polygenic risk score
    • Population based

    Fingerprint

    Dive into the research topics of 'Polygenic Risk Scores for Developmental Disorders, Neuromotor Functioning During Infancy, and Autistic Traits in Childhood'. Together they form a unique fingerprint.

    Cite this