Evidence map›Paper›PMID 25621899›Full record

ArticleNature medicine2015

Whole-genome sequencing of quartet families with autism spectrum disorder.

Ryan K C Yuen, Bhooma Thiruvahindrapuram, Daniele Merico, Susan Walker, Kristiina Tammimies, Ny Hoang, Christina Chrysler, Thomas Nalpathamkalam, Giovanna Pellecchia, Yi Liu and 18 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 290 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
290citing papers in PubMed, 5 pooled it
43.9field-weighted citation impact, top 1% of its field
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

290 citing papers in PubMed, 5 syntheses or guidelines pooled it, 540 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Review
  7. Article
  8. Article
  9. Male-Biased Social Deficits in Chd8Neuroscience bulletin · 2026
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  13. Frontiers in molecular neuroscience · 2026
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  14. Article
  15. Genomic landscape of autism spectrum disorder in Brazil.Genetics and molecular biology · 2026
    Article
  16. Article
  17. NoncodingiScience · 2025
    Article
  18. Article
  19. Article
  20. Article

230 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 2 countries.

Ryan K C YuenThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Bhooma ThiruvahindrapuramThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Daniele MericoThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Susan WalkerThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Kristiina Tammimies1] The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Women's and Children's Health, Pediatric Neuropsychiatry Unit, Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Karolinska Institutet, Stockholm, Sweden.
Ny HoangDepartment of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Christina ChryslerDepartment of Psychiatry and Behavioural Neurosciences, Offord Centre for Child Studies, McMaster University, Hamilton, Ontario, Canada.
Thomas NalpathamkalamThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Giovanna PellecchiaThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Yi Liu1] The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Jinan Pediatric Research Institute, Qilu Children's Hospital of Shandong University, Shandong, China.
Matthew J GazzelloneThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Lia D'AbateThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Eric DeneaultThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jennifer L HoweThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Richard S C LiuThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Ann ThompsonDepartment of Psychiatry and Behavioural Neurosciences, Offord Centre for Child Studies, McMaster University, Hamilton, Ontario, Canada.
Mehdi ZarreiThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Mohammed UddinThe Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Christian R Marshall1] The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Molecular Genetics, Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Robert H RingAutism Speaks, Princeton, New Jersey, USA.
Lonnie ZwaigenbaumDepartment of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Peter N RayDepartment of Molecular Genetics, Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Rosanna Weksberg1] Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. [2] Department of Paediatrics and Genetics and Genome Biology Program, The Hospital for Sick Children and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Melissa T Carter1] Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. [2] Autism Research Unit, The Hospital for Sick Children, Toronto, Ontario, Canada.
Bridget A Fernandez1] Disciplines of Genetics and Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. [2] Provincial Medical Genetic Program, Eastern Health, St. John's, Newfoundland, Canada.
Wendy RobertsAutism Research Unit, The Hospital for Sick Children, Toronto, Ontario, Canada.
Peter Szatmari1] Autism Research Unit, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Child Youth and Family Services, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. [3] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Stephen W Scherer1] The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, Ontario, Canada.
Hospital for Sick Children · CAUniversity of Toronto · CAMcMaster University · CAAutism Speaks · USMemorial University of Newfoundland · CAUniversity of Alberta · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Autism spectrum disorder (ASD) is genetically heterogeneous, with evidence for hundreds of susceptibility loci. Previous microarray and exome-sequencing studies have examined portions of the genome in simplex families (parents and one ASD-affected child) having presumed sporadic forms of the disorder. We used whole-genome sequencing (WGS) of 85 quartet families (parents and two ASD-affected siblings), consisting of 170 individuals with ASD, to generate a comprehensive data resource encompassing all classes of genetic variation (including noncoding variants) and accompanying phenotypes, in apparently familial forms of ASD. By examining de novo and rare inherited single-nucleotide and structural variations in genes previously reported to be associated with ASD or other neurodevelopmental disorders, we found that some (69.4%) of the affected siblings carried different ASD-relevant mutations. These siblings with discordant mutations tended to demonstrate more clinical variability than those who shared a risk variant. Our study emphasizes that substantial genetic heterogeneity exists in ASD, necessitating the use of WGS to delineate all genic and non-genic susceptibility variants in research and in clinical diagnostics.

Indexed as

ParentsSequence Analysis, DNASiblingsAdultChildChild Development Disorders, PervasiveFemaleGenetic Predisposition to DiseaseHumansMale

Identifiers

PMID25621899
OpenAlexW1999204296

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.