Potential role for immune-related genes in autism spectrum disorders: Evidence from genome-wide association meta-analysis of autistic traits
By: Arenella, Martina.
Contributor(s): Bellgrove, Mark A | Bralten, Janita | Buitelaar, Jan K | Cadby, Gemma | De Witte, Ward | Fornito, Alex | Hawi, Ziarih | Johnson, Beth | Jones, Rachel M | Kiemeney, Lambertus A | Moses, Eric K | Poelmans, Geert | Tiego, Jeggan | Whitehouse, Andrew JO.
Series: Autism 26 (2) 361-372: 2022. 2022Disc region: text file PDF rda.Content type: text Media type: computer Carrier type: online resource Online resources: Read this Article Summary: 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 type | Current library | Call number | Status | Date due | Barcode | Item holds | |
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Article Research | IHC Library | Available (Article available on request) | 77/13623613211019547 |
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.
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