Sub-diagnostic effects of genetic variants associated with autism

Rolland, Thomas; Cliquet, Freddy; Anney, Richard; Traut, Nicolas; Mathieu, Alexandre; Huguet, Guillaume; Cs, Leblond; Douard, Élise; Amsellem, Frédérique; Malesys, Simon; Maruani, Anna; Toro, Roberto; Packer, Alan; Wk, Chung; Jacquemont, Sébastien; Delorme, Richard; Bourgeron, Thomas

doi:10.1101/2021.02.12.21251621

Cited by 5 publications

(8 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neither of these observations are true for ICVF. Although both common and rare genetic variants are associated with autism, questions still remain if these two broad classes of variants lead to the same phenotype in the brain [23, 25] and are enriched in the same biological processes [73]. The differential overlap between rare-genetic variants and common genetic variants for autism with SA and ICVF respectively, suggests, partly different neurological effects.…”

Section: Discussionmentioning

confidence: 99%

“…A small number of studies have investigated the neural correlates of common genetic variants associated with autism, indexed by polygenic scores (PGS). These studies demonstrated that PGS for autism is associated with global and regional alterations in cortical volume, cortical thickness (CT), and surface area (SA) [18, 25]. Of which, the PGS for autism association with CT is modified by age [26].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polygenic scores for autism are associated with neurite density in adults and children from the general population

Gu,

Maria-Stauffer,

Bedford

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Genetic variants linked to autism are thought to change cognition and behaviour by altering the structure and function of the brain. Although a substantial body of literature has identified structural brain differences in autism, it is unknown whether autism-associated common genetic variants are linked to changes in cortical macro- and micro-structure. We investigated this using neuroimaging and genetic data from adults (UK Biobank, N = 31,748) and children (ABCD, N = 4,928). Using polygenic scores and genetic correlations we observe a robust negative association between common variants for autism and a magnetic resonance imaging derived phenotype for neurite density (intracellular volume fraction) in the general population. This result is consistent across both children and adults, in both the cortex and in white matter tracts, and confirmed using polygenic scores and genetic correlations. There were no sex differences in this association. Mendelian randomisation analyses provide no evidence for a causal relationship between autism and intracellular volume fraction, although this should be revisited using better powered instruments. Overall, this study provides evidence for shared common variant genetics between autism and cortical neurite density.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polygenic scores for autism are associated with neurite density in adults and children from the general population

Gu,

Maria-Stauffer,

Bedford

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…To be eligible, participants need to be over 2 years of age and have a diagnosed rare genetic condition associated with autism and/or have a diagnosis of autism (see figure 2). Decisions regarding which conditions and genetic variants to include have been made on the basis of published literature (36) and discussions with experts in the field (TB, LG), with consideration given to the penetrance, prevalence, and association with autism. For participants with a diagnosis of autism only, and where existing genetic information is available, recruitment will prioritise individuals within multiplex families and individuals with genetic variants associated with autism (see figure 2).…”

Section: Methods and Analysismentioning

confidence: 99%

European Autism GEnomics Registry (EAGER): Protocol for a multicentre cohort study and registry

Bloomfield,

Lautarescu,

Heraty

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Introduction: Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical, and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and genetic profiles. Methods and analysis: EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1,500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will give a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent for the study to access pre-existing clinical data. Participants will be added to the EAGER registry. Data will be shared via the Autism Sharing Initiative, a new international collaboration aiming to create a federated system for autism data sharing. Ethics and dissemination: EAGER has received full ethical approval from ethics committees in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023) and Spain (HCB/2023/0038, PIC-164-22). Approvals are in the process of being obtained from committees in Italy, Sweden, Ireland, and France. Findings will be disseminated via scientific publications and conferences, but also beyond to participants and the wider community (e.g., the AIMS-2-TRIALS website, stakeholder meetings, newsletters).

show abstract

“…FOXP1 (forkhead box protein P1) [136][137][138][139]. SYNGAP1 (synaptic Ras GTPase-activating protein 1) [140,141]. GABRA5 (gamma-aminobutyric acid type A receptor subunit alpha5) [142,143].…”

Section: Genes and Geneticsmentioning

confidence: 99%

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer’s Disease

et al. 2021

View full text Add to dashboard Cite

Autism spectrum disorder (ASD) and Alzheimer’s disease (AD) are neurodevelopmental and neurodegenerative disorders affecting two opposite ends of life span, i.e., childhood and old age. Both disorders pose a cumulative threat to human health, with the rate of incidences increasing considerably worldwide. In the context of recent developments, we aimed to review correlated symptoms and genetics, and overlapping aspects in the mechanisms of the pathogenesis of ASD and AD. Dementia, insomnia, and weak neuromuscular interaction, as well as communicative and cognitive impairments, are shared symptoms. A number of genes and proteins linked with both disorders have been tabulated, including MECP2, ADNP, SCN2A, NLGN, SHANK, PTEN, RELN, and FMR1. Theories about the role of neuron development, processing, connectivity, and levels of neurotransmitters in both disorders have been discussed. Based on the recent literature, the roles of FMRP (Fragile X mental retardation protein), hnRNPC (heterogeneous ribonucleoprotein-C), IRP (Iron regulatory proteins), miRNAs (MicroRNAs), and α-, β0, and γ-secretases in the posttranscriptional regulation of cellular synthesis and processing of APP (amyloid-β precursor protein) have been elaborated to describe the parallel and overlapping routes and mechanisms of ASD and AD pathogenesis. However, the interactive role of genetic and environmental factors, oxidative and metal ion stress, mutations in the associated genes, and alterations in the related cellular pathways in the development of ASD and AD needs further investigation.

show abstract

Sub-diagnostic effects of genetic variants associated with autism

Cited by 5 publications

References 90 publications

Polygenic scores for autism are associated with neurite density in adults and children from the general population

Polygenic scores for autism are associated with neurite density in adults and children from the general population

European Autism GEnomics Registry (EAGER): Protocol for a multicentre cohort study and registry

Symptomatic, Genetic, and Mechanistic Overlaps between Autism and Alzheimer’s Disease

Contact Info

Product

Resources

About