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Record W4382139278 · doi:10.1038/s41591-023-02408-2

Phenotypic effects of genetic variants associated with autism

2023· article· en· W4382139278 on OpenAlexafffund
Thomas Rolland, Freddy Cliquet, Richard Anney, Clara Moreau, Nicolas Traut, Alexandre Mathieu, Guillaume Huguet, Jinjie Duan, Varun Warrier, Swan Portalier, Louise Dry, Claire S. Leblond, Élise Douard, Frédérique Amsellem, Simon Malesys, Anna Maruani, Roberto Toro, Anders D. Børglum, Jakob Grove, Simon Baron‐Cohen, Alan Packer, Wendy K. Chung, Sébastien Jacquemont, Richard Delorme, Thomas Bourgeron

Bibliographic record

VenueNature Medicine · 2023
Typearticle
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsUniversité de MontréalCentre Hospitalier Universitaire Sainte-Justine
FundersCanadian Institutes of Health ResearchNational Institutes of HealthUniversité de ParisInstitut de Valorisation des DonnéesH. Lundbeck A/SAutism SpeaksCanada First Research Excellence FundMedical Research CouncilMedical Research Council CanadaUniversité Paris DiderotAgence Nationale de la RechercheKøbenhavns UniversitetNational Institute for Health and Care ResearchConny-Maeva Charitable FoundationUK Research and InnovationInnovative Medicines InitiativeInstitut PasteurCompute CanadaLundbeckfondenSimons FoundationGovernment of the United KingdomMedical Research FoundationHORIZON EUROPE Framework ProgrammeAutisticaEuropean Federation of Pharmaceutical Industries and AssociationsNIHR Cambridge Biomedical Research CentreTempleton World Charity FoundationWellcomeEuropean CommissionNational Institute of Mental HealthHorizon 2020 Framework ProgrammeAarhus UniversitetFondation Bettencourt SchuellerWellcome TrustSimons Foundation Autism Research Initiative
KeywordsPhenotypeGeneticsAutismBiologyComputational biologyMedicineGenePsychiatry

Abstract

fetched live from OpenAlex

While over 100 genes have been associated with autism, little is known about the prevalence of variants affecting them in individuals without a diagnosis of autism. Nor do we fully appreciate the phenotypic diversity beyond the formal autism diagnosis. Based on data from more than 13,000 individuals with autism and 210,000 undiagnosed individuals, we estimated the odds ratios for autism associated to rare loss-of-function (LoF) variants in 185 genes associated with autism, alongside 2,492 genes displaying intolerance to LoF variants. In contrast to autism-centric approaches, we investigated the correlates of these variants in individuals without a diagnosis of autism. We show that these variants are associated with a small but significant decrease in fluid intelligence, qualification level and income and an increase in metrics related to material deprivation. These effects were larger for autism-associated genes than in other LoF-intolerant genes. Using brain imaging data from 21,040 individuals from the UK Biobank, we could not detect significant differences in the overall brain anatomy between LoF carriers and non-carriers. Our results highlight the importance of studying the effect of the genetic variants beyond categorical diagnosis and the need for more research to understand the association between these variants and sociodemographic factors, to best support individuals carrying these variants.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.896
Threshold uncertainty score0.441

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.291
Teacher spread0.278 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations81
Published2023
Admission routes2
Has abstractyes

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