146217 - potential role for immune related.pdf (543 kB)
Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits
journal contribution
posted on 2023-05-21, 01:51 authored by Arenella, M, Cadby, G, De Witte, W, Jones, RM, Whitehouse, AJO, Eric MosesEric Moses, Fornito, A, Bellgrove, MA, Hawi, Z, Johnson, B, Tiego, J, Buitelaar, JK, Kiemeney, LA, Poelmans, G, Bralten, JThe 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.
History
Publication title
AutismPagination
1-12ISSN
1362-3613Department/School
Menzies Institute for Medical ResearchPublisher
Sage Publications Ltd.Place of publication
United KingdomRights statement
© The Author(s) 2021. Creative Commons Attribution 4.0 International (CC BY 4.0) License, (https://creativecommons.org/licenses/by/4.0/)Repository Status
- Open