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Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits


Arenella, M and Cadby, G and De Witte, W and Jones, RM and Whitehouse, AJO and Moses, EK and Fornito, A and Bellgrove, MA and Hawi, Z and Johnson, B and Tiego, J and Buitelaar, JK and Kiemeney, LA and Poelmans, G and Bralten, J, Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits, Autism pp. 1-12. ISSN 1362-3613 (2021) [Refereed Article]

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© The Author(s) 2021. Creative Commons Attribution 4.0 International (CC BY 4.0) License, (

DOI: doi:10.1177/13623613211019547


The clinical heterogeneity of autism spectrum disorders majorly challenges their genetic study. Autism spectrum disorders symptoms occur in milder forms in the general population, as autistic-like traits, and share genetic factors with autism spectrum disorders. Here, we investigate the genetics of individual autistic-like traits to improve our understanding of autism spectrum disorders. We meta-analysed four population-based genome-wide association studies investigating four autistic-like traits – ‘attention-to-detail’, ‘imagination’, ‘rigidity’ and ‘social-skills’ (n=4600). Using autism spectrum disorder summary statistics from the Psychiatric Genomic Consortium (N=46,350), we applied polygenic risk score analyses to understand the genetic relationship between autism spectrum disorders and autistic-like traits. Using MAGMA, we performed gene-based and gene co-expression network analyses to delineate involved genes and pathways. We identified two novel genome-wide significant loci – rs6125844 and rs3731197 – associated with ‘attention-to-detail’. We demonstrated shared genetic aetiology between autism spectrum disorders and ‘rigidity’. Analysing top variants and genes, we demonstrated a role of the immune-related genes RNF114, CDKN2A, KAZN, SPATA2 and ZNF816A in autistic-like traits. Brain-based genetic expression analyses further linked autistic-like traits to genes involved in immune functioning, and neuronal and synaptic signalling. Overall, our findings highlight the potential of the autistic-like trait– based approach to address the challenges of genetic research in autism spectrum disorders. We provide novel insights showing a potential role of the immune system in specific autism spectrum disorder dimensions.

Item Details

Item Type:Refereed Article
Keywords:autism spectrum disorders, genetics, immune system, molecular and cellular biology
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Genetic immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Moses, EK (Professor Eric Moses)
ID Code:146217
Year Published:2021
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-08-25
Last Modified:2022-08-23
Downloads:16 View Download Statistics

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