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De novo network analysis reveals autism causal genes and developmental links to co-occurring traits.

ABSTRACT: 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, and RP11-798G7.6). LINC02210 was 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.

SUBMITTER: Miller CJ

PROVIDER: S-EPMC10410065 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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De novo network analysis reveals autism causal genes and developmental links to co-occurring traits.

Miller Catriona J CJ Golovina Evgeniia E Wicker Joerg S JS Jacobsen Jessie C JC O'Sullivan Justin M JM

Life science alliance 20230808 10

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 ...[more]

PMID: 37553252

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Project description:Gastrointestinal (GI) symptoms are frequently reported in children with autism spectrum disorder (ASD). We evaluated the frequency and severity of GI symptoms in preschool-aged children with ASD compared to participants with typical development (TD). Our goal was to ascertain whether GI symptoms are associated with differences in sex or developmental and behavioral measures. Participants were between 2 and 3.5 years of age and included 255 children with ASD (184 males/71 females) and 129 age-matched TD controls (75 males/54 females). A parent interview was used to assess GI symptoms (abdominal pain, gaseousness/bloating, diarrhea, constipation, pain on stooling, vomiting, difficulty swallowing, blood in stool or in vomit). Children with GI symptoms in each diagnostic group were compared to children without GI symptoms on measures of developmental, behavioral, and adaptive functioning. GI symptoms were reported more frequently in children with ASD compared to the TD group (47.8% vs. 17.8%, respectively). Children with ASD were also more likely to experience multiple GI symptoms (30.6% vs. 5.4%). GI symptoms were equally common in males and females across both diagnostic groups. There were no statistically significant differences in developmental or adaptive measures based on presence of GI symptoms in either ASD or TD children. Co-occurring GI symptoms were, however, associated with increased self-injurious behaviors, restricted stereotyped behaviors, aggressive behaviors, sleep problems and attention problems in both ASD and TD children. In children with ASD, a higher number of GI symptoms was associated with an increase in self-injurious behaviors, somatic complaints, reduced sleep duration, and increased parasomnias. LAY SUMMARY: ASD is characterized by challenges in social communication and repetitive behaviors. But, people with autism have many other difficulties including gastrointestinal problems. Children with ASD were three times more likely to experience GI symptoms than typically developing peers. Increased GI symptoms are associated with increased problem behaviors such as sleep problems, self-injury, and body aches. Since GI symptoms are often treatable, it is important to recognize them as soon as possible. Both clinicians and parents should become more aware of the high occurrence of GI problems in autistic people. Autism Res 2020, 13: 1778-1789. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Dataset Information

De novo network analysis reveals autism causal genes and developmental links to co-occurring traits.

Publications

De novo network analysis reveals autism causal genes and developmental links to co-occurring traits.

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