Identifying the neurodevelopmental and psychiatric signatures of genomic disorders associated with intellectual disability: a machine learning approach

Nicholas Donnelly, Adam Cunningham, Sergio Marco Salas, Matthew Bracher-Smith, Samuel Chawner, Jan Stochl, Tamsin J. Ford, F. Lucy Raymond, Valentina Escott-Price, Marianne B.M. van den Bree*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
42 Downloads (Pure)

Abstract

Background
Genomic conditions can be associated with developmental delay, intellectual disability, autism spectrum disorder, and physical and mental health symptoms. They are individually rare and highly variable in presentation, which limits the use of standard clinical guidelines for diagnosis and treatment. A simple screening tool to identify young people with genomic conditions associated with neurodevelopmental disorders (ND-GCs) who could benefit from further support would be of considerable value. We used machine learning approaches to address this question.

Method
A total of 493 individuals were included: 389 with a ND-GC, mean age = 9.01, 66% male) and 104 siblings without known genomic conditions (controls, mean age = 10.23, 53% male). Primary carers completed assessments of behavioural, neurodevelopmental and psychiatric symptoms and physical health and development. Machine learning techniques (penalised logistic regression, random forests, support vector machines and artificial neural networks) were used to develop classifiers of ND-GC status and identified limited sets of variables that gave the best classification performance. Exploratory graph analysis was used to understand associations within the final variable set.

Results
All machine learning methods identified variable sets giving high classification accuracy (AUROC between 0.883 and 0.915). We identified a subset of 30 variables best discriminating between individuals with ND-GCs and controls which formed 5 dimensions: conduct, separation anxiety, situational anxiety, communication and motor development.

Limitations
This study used cross-sectional data from a cohort study which was imbalanced with respect to ND-GC status. Our model requires validation in independent datasets and with longitudinal follow-up data for validation before clinical application.

Conclusions
In this study, we developed models that identified a compact set of psychiatric and physical health measures that differentiate individuals with a ND-GC from controls and highlight higher-order structure within these measures. This work is a step towards developing a screening instrument to identify young people with ND-GCs who might benefit from further specialist assessment.
Original languageEnglish
Article number19
JournalMolecular Autism
Volume14
Issue number1
DOIs
Publication statusPublished - 23 May 2023

Bibliographical note

Funding Information:
This research was funded by the Baily Thomas Charitable Fund (TRUST/VC/AC/SG/5196-8188; MvdB), and NIMH (U01 MH119738-01; MvdB), an NIHR clinical lectureship award (NAD), and SJRAC is funded by a Medical Research Foundation Fellowship (MRF-058-0015-F-CHAW). The IMAGINE-ID study (MvdB) was funded by Medical Research Council Grants MR/L011166/1, MR/T033045/1 and MR/N022572/1.

Publisher Copyright:
© 2023, The Author(s).

Keywords

  • Behavioural phenotypes
  • Genetic syndromes
  • Intellectual disability
  • Machine learning

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