Evidence map›Paper›PMID 29890955›Full record

ArticleJournal of neurodevelopmental disorders2018

A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees.

Marc Woodbury-Smith, Andrew D Paterson, Irene O'Connor, Mehdi Zarrei, Ryan K C Yuen, Jennifer L Howe, Ann Thompson, Morgan Parlier, Bridget Fernandez, Joseph Piven and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurodevelopmental disorders, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
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  3. Review
  4. ReducedFrontiers in cell and developmental biology · 2022
    Article
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  7. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Marc Woodbury-SmithInstitute of Neuroscience, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK. marc.woodbury-smith@newcastle.ac.uk.ORCID 0000-0002-0593-8917
Andrew D PatersonProgram in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Irene O'ConnorDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
Mehdi ZarreiProgram in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Ryan K C YuenProgram in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Jennifer L HoweProgram in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Ann ThompsonDepartment of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
Morgan ParlierCarolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA.
Bridget FernandezProvincial Medical Genetics Program, Health Sciences Centre, St. John's, Newfoundland, Canada.
Joseph PivenCarolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, NC, USA.
Stephen W SchererProgram in Genetics and Genome Biology, The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Veronica VielandBattelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
Peter SzatmariCentre for Addiction and Mental Health, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada.

Funding

UNC MRDD Research CenterP30HD003110 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PIVEN, JOSEPH · 1985 to 2012
$28.7M
Combining epidemiologic designs to model genetic risks for psychiatric disordersR01MH086117 · NIMH · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI VIELAND, VERONICA J. · 2009 to 2011
$2.7M
A Molecular Genetic Study of Autism and Related Phenotypes in Extended PedigreesR01MH076028 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PIVEN, JOSEPH · 2006 to 2010
$2.6M
CIHR 79499CIHR 89777NICHD NIH HHS P30 HD003110NIMH NIH HHS R01 MH076028NIMH NIH HHS R01 MH086117Wellcome Trust
6 · The paper itself

Abstract

backgroundAlthough several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees.

methodsASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale.

resultsThe results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent.

conclusionsInclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity.

Indexed as

Genetic LinkageAdolescentAdultAgedAged, 80 and overAutism Spectrum DisorderBayes TheoremCanadaChildChild, PreschoolChromosomesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInfantAutism spectrum disorder (ASD)Extended pedigreesFamily geneticsGenome-wide linkagePosterior probability of linkage (PPL)

Identifiers

PMID29890955
PMCPMC5996536

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.