Potential Role for Immune-Related Genes in Autism Spectrum Disorders: Evidence from Genome-Wide Association Meta-Analysis of Autistic Traits

Autor/inn/en	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
Titel	Potential Role for Immune-Related Genes in Autism Spectrum Disorders: Evidence from Genome-Wide Association Meta-Analysis of Autistic Traits
Quelle	In: Autism: The International Journal of Research and Practice, 26 (2022) 2, S.361-372 (12 Seiten) PDF als Volltext Verfügbarkeit
Zusatzinformation	ORCID (Bralten, Janita)
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1362-3613
DOI	10.1177/13623613211019547
Schlagwörter	Autism; Pervasive Developmental Disorders; Genetics; Symptoms (Individual Disorders); Attention; Etiology; Imagination; Cognitive Processes; Interpersonal Competence + Suchen Sie Ihr Suchwort? Autismus; Humangenetik; Psychiatrische Symptomatik; Aufmerksamkeit; Ätiologie; Cognitive process; Kognitiver Prozess; Interpersonale Kompetenz
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. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2024/1/01