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Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits
Citation
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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Copyright Statement
© The Author(s) 2021. Creative Commons Attribution 4.0 International (CC BY 4.0) License, (https://creativecommons.org/licenses/by/4.0/)
DOI: doi:10.1177/13623613211019547
Abstract
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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