Genetic liability to rheumatoid arthritis on autism and autistic traits: polygenic risk score and Mendelian randomization analyses

Higher prevalence of autism in offspring born to mothers with rheumatoid arthritis has been reported in observational studies. We investigated (a) the associations between maternal and offspring’s own genetic liability for rheumatoid arthritis and autism-related outcomes in the offspring using polygenic risk scores (PRS) and (b) whether the effects were causal using Mendelian randomization (MR). Using the latest genome-wide association (GWAS) summary data on rheumatoid arthritis and individual-level data from the Avon Longitudinal Study of Parents and Children, United Kingdom, we constructed PRSs for maternal and offspring genetic liability for rheumatoid arthritis (single-nucleotide polymorphism [SNP] p-value threshold 0.05). We investigated associations with autism, and autistic traits: social and communication difficulties, coherence, repetitive behaviours and sociability. We used modified Poisson regression with robust standard errors. In two-sample MR analyses, we used 40 genome-wide significant SNPs for rheumatoid arthritis and investigated the causal effects on risk for autism, in 18,381 cases and 27,969 controls of the Psychiatric Genetics Consortium and iPSYCH. Sample size ranged from 4992 to 7849 in PRS analyses. We found little evidence of associations between rheumatoid arthritis PRSs and autism-related phenotypes in the offspring (maternal PRS on autism: RR 0.89, 95%CI 0.73–1.07, p = 0.21; offspring’s own PRS on autism: RR 1.11, 95%CI 0.88–1.39, p = 0.39). MR results provided little evidence for a causal effect (IVW OR 1.01, 95%CI 0.98–1.04, p = 0.56). There was little evidence for associations between genetic liability for rheumatoid arthritis on autism-related outcomes in offspring. Lifetime risk for rheumatoid arthritis has no causal effects on autism.

Dimensions of Self-Reported Driving Difficulty in Autistic and Non-Autistic Adults and their Relationship with Autistic Traits

A survey asked autistic and non-autistic people about the driving difficulties they experience and their autistic traits. Principle components analysis was used to identify how reported difficulties clustered together in each group, and regression was used to determine which subscales of the Autism Spectrum Quotient predict these factors. For autistic drivers three factors of driving difficulty emerged: a Driving Executive factor, predicted by Attention Switching; a Driving Understanding factor, predicted by Communication; and a Driving Social Interaction factor, predicted by Attention Switching. For non-autistic drivers only one Driving General factor emerged, predicted by Communication. This suggests autistic people may experience at least three distinct domains of difficulty when driving which may relate to their particular profile of autistic features.

The use of a tablet-based app for investigating the influence of autistic and ADHD traits on performance in a complex drawing task

This paper describes a smart tablet-based drawing app to digitally record participants’ engagement with the Rey-Osterrieth complex figure (ROCF) task, a well-characterised perceptual memory task that assesses local and global memory. Digitisation of the tasks allows for improved ecological validity, especially in children attracted to tablet devices. Further, digital translation of the tasks affords new measures, including accuracy and computation of the fine motor control kinematics employed to carry out the drawing Here, we report a feasibility study to test the relationship between two neurodevelopmental conditions: autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The smart tablet app was employed with 39 adult participants (18-35) characterised for autistic and ADHD traits, and scored using the ROCF perceptual and organisational scoring systems. Trait scores and conditions were predictor variables in linear regression models. Positive correlations were found between the attention-to-detail, attention-switching and communication subscales of the autistic trait questionnaire and organisational scores on the ROCF task. These findings suggest that autistic traits might be linked to differential performance on the ROCF task. Novelty and future applications of the app are discussed.

Case report of a de novo mutation of PCDH19 in Saudi family limited to females

Up to date more than 60 different mutations in PCDH19 have been identified. Most of PCDH19 gene is located in Xq22 and produces nonclustered delta protocadherin. This disorder primarily manifests in heterozygote females due to random X chromosome inactivation leading to somatic mosaicism and abnormal cellular interference between cells with and without delta-protocadherin., but we a heterozygous nucleotide mutation causing amino acid 561 to change from Pro to Ser (p.Pro561Ser). This mutation was de novo, and this alteration was not found in her parents. PCDH19-related epilepsy is a distinct childhood-onset epilepsy syndrome characterized by brief clusters of febrile and afebrile seizures with onset primarily before the age of three years, cognitive impairment, autistic traits, and behavioral abnormalities. We describe the features of a de novo mutation in 3 sibling, presented with early onset of seizure, two of them were controlled and wean off medication was at age of six year and her sister at age of 10 year .The youngest sister still partially controlled on medication, she had seizure only during febrile illness.