ERIC Number: EJ1328477
Record Type: Journal
Publication Date: 2022-Feb
Pages: 12
Abstractor: As Provided
ISBN: N/A
ISSN: ISSN-1362-3613
EISSN: N/A
Potential Role for Immune-Related Genes in Autism Spectrum Disorders: Evidence from Genome-Wide Association Meta-Analysis of Autistic Traits
Arenella, Martina; Cadby, Gemma; De Witte, Ward; Jones, Rachel M.; Whitehouse, Andrew J. O.; Moses, Eric K.; Fornito, Alex; Bellgrove, Mark A.; Hawi, Ziarih; Johnson, Beth; Tiego, Jeggan; Buitelaar, Jan K.; Kiemeney, Lambertus A.; Poelmans, Geert; Bralten, Janita
Autism: The International Journal of Research and Practice, v26 n2 p361-372 Feb 2022
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.
Descriptors: Autism, Pervasive Developmental Disorders, Genetics, Symptoms (Individual Disorders), Attention, Etiology, Imagination, Cognitive Processes, Interpersonal Competence
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Publication Type: Journal Articles; Reports - Research
Education Level: N/A
Audience: N/A
Language: English
Sponsor: N/A
Authoring Institution: N/A
Grant or Contract Numbers: N/A