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Record W2100242214 · doi:10.1093/hmg/dds301

Individual common variants exert weak effects on the risk for autism spectrum disorders

2012· article· en· W2100242214 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueHuman Molecular Genetics · 2012
Typearticle
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsUniversity of British ColumbiaUniversity of AlbertaUniversity of ManitobaMcGill UniversityMemorial University of NewfoundlandMcMaster UniversityUniversity of Toronto
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeNational Institute of Mental HealthOntario Ministry of Research and InnovationMedical Research CouncilCanadian Institutes of Health ResearchHospital for Sick ChildrenMinistero della SaluteInstitut National de la Santé et de la Recherche MédicaleFondation de FranceHealth Research BoardNational Institute for Health and Care ResearchOntario Genomics InstituteFondation OrangeKoninklijke Nederlandse Akademie van WetenschappenHussman FoundationAutism SpeaksSick Kids FoundationNational Institutes of HealthOntario GenomicsGenome CanadaNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustScience Foundation IrelandDeutsche ForschungsgemeinschaftGlaxoSmithKlineOntario Innovation TrustUniversity of Toronto
KeywordsSingle-nucleotide polymorphismAutismGeneticsGenome-wide association studyGenetic associationSNPAlleleBiologyGenetic architectureGenotypingMinor allele frequencyCopy-number variationGenotypeGenePhenotypeGenomePsychologyDevelopmental psychology

Abstract

fetched live from OpenAlex

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.

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.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.549
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.029
GPT teacher head0.299
Teacher spread0.270 · 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