Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other neurological disorders, such as ADHD, anxiety, and schizophrenia, which can complicate diagnosis and management. While research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood. To address this gap, we conducted a two-sample Mendelian Randomisation analysis and identified four genes located at the 17q21.31 locus that are causally linked to autism in fetal cortical tissue (i.e. LINC02210, LRRC37A4P, RP11-259G18.1, RP11-798G7.6). LINC02210 was also identified as being causally related to autism in adult cortical tissue. By integrating data from expression quantitative trait loci [eQTLs], genes, and protein interactions we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits and conditions in fetal cortical tissue. We also identified an additional distinct cluster of co-occurring traits, including cognition and worry, linked to genetic loci at 3p21.1. Our results support the hypothesis that an individual's autism phenotype is partially determined by their genetic risk for co-occurring conditions. Overall, our findings provide insights into the complex relationship between autism and co-occurring conditions, which could be used to develop predictive models for more accurate diagnosis and better clinical management.

Autism is a complex neurodevelopmental condition that manifests in various ways. Autism is often accompanied by other conditions, such as attention-deficit/hyperactivity disorder and schizophrenia, which can complicate diagnosis and management. Although research has investigated the role of specific genes in autism, their relationship with co-occurring traits is not fully understood. To address this, we conducted a two-sample Mendelian randomisation analysis and identified four genes located at the 17q21.31 locus that are putatively causal for autism in fetal cortical tissue (LINC02210,LRRC37A4P,RP11-259G18.1, andRP11-798G7.6).LINC02210was also identified as putatively causal for autism in adult cortical tissue. By integrating data from expression quantitative trait loci, genes and protein interactions, we identified that the 17q21.31 locus contributes to the intersection between autism and other neurological traits in fetal cortical tissue. We also identified a distinct cluster of co-occurring traits, including cognition and worry, linked to the genetic loci at 3p21.1. Our findings provide insights into the relationship between autism and co-occurring traits, which could be used to develop predictive models for more accurate diagnosis and better clinical management.