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The following is a summary of “Exploring autism spectrum disorder and co-occurring trait associations to elucidate multivariate genetic mechanisms and insights,” published in the December 2024 issue of Psychiatry by Salenius et al.

Autism spectrum disorder (ASD) is a neurodevelopmental trait with partial heritability, often co-occurring with conditions like ADHD, anxiety, and learning difficulties. Complex genetic and environmental factors influence the development of ASD using multivariate genome-wide association studies (GWAS). 

Researchers conducted a retrospective study to explore the genetic mechanisms underlying ASD and its co-occurring traits.  

They conducted the largest multivariate GWAS to date on ASD and 8 co-occurring traits (ADHD, childhood ADHD, anxiety stress (ASDR), bipolar (BIP), disruptive behavior (DBD), educational attainment (EA), major depression, and schizophrenia (SCZ)) using summary statistics from leading studies. They performed colocalization and Mendelian randomization (MR) analysis on associations with central traits containing ASD and validated the findings with pathway and QTL resources, as well as independent datasets consisting of 112 whole genome sequences (45 probands) from the GEMMA project. 

The results showed 637 significant associations (P < 5e-8), with 322 reported for the first time. About 37 SNPs contained ASD and 1 or more traits in their central trait set, including MAPT, CADPS, NEGR1, KANSL1, NSF, and NTM genes. Mendelian randomization found genetic liability for ADHD childhood, ASRD, and DBT has causal effects on ASD, while ASD genetic liability affects ADHD, ADHD childhood, BIP, WA, MDD, and SCZ. Frequency differences in SNPs from NTM and CADPS were found between GEMMA ASD probands and controls. Pathway, QTL, and cell type enrichment highlighted microbiome, enteric inflammation, and central nervous system enrichments. 

Investigators identified novel genetic associations related to ASD and its co-occurring traits, expanding the understanding of its complex genetics. The findings provided insights into neuronal brain disruptions potentially driving ASD development and manifestation. 

Source: bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-06392-w#Abs1