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Record W2152157708 · doi:10.1093/hmg/ddq307

A genome-wide scan for common alleles affecting risk for autism

2010· article· en· W2152157708 on OpenAlexafffund
Richard Anney, Lambertus Klei, Dalila Pinto, Regina Regan, Jennifer Conroy, Tiago R. Magalhães, Catarina Correia, Brett S. Abrahams, N. Sykes, A. T. Pagnamenta, J.-P. de Almeida, Elena Bacchelli, Anthony Bailey, Gillian Baird, Agatino Battaglia, T. P. Berney, Nadia Bolshakova, Sven Bölte, P. F. Bolton, Thomas Bourgeron, S. Brennan, Jessica Brian, A. R. Carson, Guillermo Casallo, Jillian P. Casey, Su H. Chu, Lynne Cochrane, Christina Corsello, E. L. Crawford, A. Crossett, Géraldine Dawson, Maretha Jonge, Richard Delorme, Irene Drmic, Eftichia Duketis, Frederico Duque, Annette Estes, Penny Farrar, Bridget A. Fernandez, Susan E. Folstein, Éric Fombonne, Christine M. Freitag, James Gilbert, Joseph Glessner, Joel O. Goldberg, Jonathan Green, Stephen J. Guter, Håkon Håkonarson, Elizabeth A. Heron, Matthew Hill, Richard Holt, Jennifer Howe, Gillian Hughes, Vanessa Hus, Roberta Igliozzi, C. Kim, Sabine M. Klauck, Alexander Kolevzon, Olena Korvatska, Vlad Kustanovich, Clara Lajonchere, Janine A. Lamb, Magdalena Laskawiec, Marion Leboyer, Ann Le Couteur, Bennett Leventhal, A. C. Lionel, Xiaoqing Liu, Catherine Lord, Linda Lotspeich, Sabata C. Lund, Elena Maestrini, William J. Mahoney, Carine Mantoulan, Christian R. Marshall, Helen McConachie, Christopher J. McDougle, Jane McGrath, William M. McMahon, Nadine Melhem, Alison Merikangas, Ohsuke Migita, Nancy J. Minshew, Ghazala Mirza, Jeff Munson, Stanley F. Nelson, C. Noakes, Abdul Noor, Gudrun Nygren, Guiomar Oliveira, Κaterina Papanikolaou, Jeremy Parr, Barbara Parrini, Tara Paton, Andrew Pickles, Joseph Piven, David J. Posey, Annemarie Poustka, Fritz Poustka, Aparna Prasad, Jiannis Ragoussis, Katy Renshaw, Jessica Rickaby, Wendy Roberts, Kathryn Roeder, Bernadette Rogé, Michael Rutter, Laura J. Bierut, John P. Rice, Jeff Salt, Katherine Sansom, Daisuke Sato, Ricardo Segurado, L. Senman, Naisha Shah, Val C. Sheffield, Latha Soorya, Inês Sousa, Vera Stoppioni, Christina P. Strawbridge, Raffaella Tancredi, Katherine E. Tansey, Bhooma Thiruvahindrapduram, A. P. Thompson, Susan Thomson, Ana Tryfon, John Tsiantis, Hermán van Engeland, John B. Vincent, Fred R. Volkmar, Simon Wallace, Kai Wang, Zhonghua Wang, Thomas H. Wassink, Kirsty Wing, Kerstin Wittemeyer, S. Wood, Brian L. Yaspan, Danielle Zurawiecki, Lonnie Zwaigenbaum, Catalina Betancur, Joseph D. Buxbaum, Rita M. Cantor, Edwin H. Cook, Hilary Coon, Michael L. Cuccaro, Louise Gallagher, Daniel H. Geschwind, Michael Gill, J.L. Haines, Judith Miller, Anthony P. Monaco, John I. Nürnberger, Andrew D. Paterson, Margaret A. Pericak‐Vance, Gerard D. Schellenberg, Stephen W. Scherer, James S. Sutcliffe, Péter Szatmári, Astrid M. Vicente, Veronica J. Vieland, Ellen M. Wijsman, Bernie Devlin, Sean Ennis, Joachim Hallmayer

Bibliographic record

VenueHuman Molecular Genetics · 2010
Typearticle
Languageen
FieldNeuroscience
TopicAutism Spectrum Disorder Research
Canadian institutionsUniversity of AlbertaMcMaster UniversityMcGill UniversityConcordia UniversityCentre for Addiction and Mental HealthMemorial University of NewfoundlandHolland Bloorview Kids Rehabilitation HospitalUniversity of TorontoSickKids FoundationHospital for Sick Children
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Neurological Disorders and StrokeNational Cancer InstituteNational Institute on Drug AbuseNational Institute of Mental HealthNational Institute on Alcohol Abuse and AlcoholismOntario Ministry of Research and InnovationMedical Research CouncilCanadian Institutes of Health ResearchFondation de FranceHospital for Sick ChildrenMinistero della SaluteInstitut National de la Santé et de la Recherche MédicaleOntario Genomics InstituteNational Human Genome Research InstituteFondation OrangeNational Institutes of HealthOntario GenomicsFondation FondaMentalKoninklijke Nederlandse Akademie van WetenschappenOntario Innovation TrustHoward Hughes Medical InstituteHussman FoundationNederlandse Organisatie voor Wetenschappelijk OnderzoekWellcome TrustGenome CanadaHealth Research BoardDeutsche ForschungsgemeinschaftGlaxoSmithKlineUniversity of TorontoAutism SpeaksSick Kids FoundationJohns Hopkins University
KeywordsBiologyGeneticsSingle-nucleotide polymorphismAutismGenome-wide association studyGenetic associationAlleleSNPGenotypeMinor allele frequencySample size determinationAllele frequencyGeneMedicine

Abstract

fetched live from OpenAlex

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0020.002
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.028
GPT teacher head0.319
Teacher spread0.291 · 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 source (direct Gemma or distilled Codex), 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

Citations588
Published2010
Admission routes2
Has abstractyes

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