Neuropsychiatric risk in children with intellectual disability of genetic origin: IMAGINE - The UK National Cohort Study

Background: Children with intellectual disability (ID) frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aimed to determine the impact of genomics, inheritance and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared to the general population. Methods: IMAGINE is a prospective study using online mental health and medical assessments in a cohort of 2770 children with ID and pathogenic genomic variants, identified by the UK’s National Health Service. Outcomes: Assessments completed on 2397 young people with ID (4-19 years, M 9·2, SD 3·9) with a rare pathogenic genomic variant. 1339 (55·9%) were male. 1771 (73·9%) of participants had a pathogenic copy number variant (CNV), 626 (26·1%) a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk of co-occurring neuropsychiatric diagnoses, compared with the UK national population, was high: Autism Spectrum Disorder 29·2 (95% CI 23·9 to 36·5), Attention Deficit Hyperactivity Disorder 13·5 (95% CI 11·1 to 16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV. Interpretation: Children with genomic variants and ID are at a greatly enhanced risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk

The genomic basis of parasitism in the Strongyloides clade of nematodes.

Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism