Evidence map›Paper›PMID 37541188›Full record

ArticleAmerican journal of human genetics2023

Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders.

Alba Sanchis-Juan, Karyn Megy, Jonathan Stephens, Camila Armirola Ricaurte, Eleanor Dewhurst, Kayyi Low, Courtney E French, Detelina Grozeva, Kathleen Stirrups, Marie Erwood and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Pangenome discovery of missing autism variants.medRxiv : the preprint server for health sciences · 2025
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. The Brain Gene Registry: a data snapshot.Journal of neurodevelopmental disorders · 2024
    Article
  13. Article
  14. Functional genomics and small molecules in mitochondrial neurodevelopmental disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024
    Review
  15. Article
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

32 authors.

Alba Sanchis-JuanDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Molecular Neurogenetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Karyn MegyDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Jonathan StephensDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Camila Armirola RicaurteDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Eleanor DewhurstDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Kayyi LowDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Courtney E FrenchClinical Medical School, University of Cambridge, Cambridge, UK.
Detelina GrozevaDepartment of Medical Genetics, University of Cambridge, Cambridge, UK; Centre for Trials Research, Cardiff University, Cardiff, UK.
Kathleen StirrupsDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Marie ErwoodDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Amy McTagueMolecular Neurosciences, Zayed Centre for Research into Rare Disease in Children, UCL Great Ormond Street Institute of Child Health, London, UK; Department of Neurology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Christopher J PenkettDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Olga ShamardinaDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Salih TunaDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Louise C DaughertyDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Nicholas GleadallDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Sofia T DuarteHospital Dona Estefânia, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
Antonio Hedrera-FernándezPediatric Neurology Department, Hospital Universitario Central de Asturias, Asturias, Spain.
Julie VogtWest Midlands Regional Genetics Service, Birmingham Women's and Children's Hospital, Birmingham, UK.
Gautam AmbegaonkarChild Development Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Manali ChitreClinical Medical School, University of Cambridge, Cambridge, UK.
Dragana JosifovaGuy's and St Thomas' Hospital, London, UK.
Manju A KurianMolecular Neurosciences, Zayed Centre for Research into Rare Disease in Children, UCL Great Ormond Street Institute of Child Health, London, UK.
Alasdair ParkerClinical Medical School, University of Cambridge, Cambridge, UK; Child Development Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Julia RankinDepartment of Clinical Genetics, Royal Devon University Healthcare NHS Foundation Trust, Exeter, UK.
Evan ReidCambridge Institute for Medical Research and Department of Medical Genetics, University of Cambridge, Cambridge, UK.
Emma WakelingNorth West Thames Regional Genetics Service, Harrow, UK.
Evangeline WassmerNeurology Department, Birmingham Women and Children's Hospital, Birmingham, UK.
C Geoffrey WoodsClinical Medical School, University of Cambridge, Cambridge, UK; Department of Medical Genetics, University of Cambridge, Cambridge, UK.
NIHR BioResource
F Lucy RaymondDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Medical Genetics, University of Cambridge, Cambridge, UK. Electronic address: flr24@cam.ac.uk.
Keren J CarssDepartment of Haematology, University of Cambridge, Cambridge, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. Electronic address: keren.carss@astrazeneca.com.

Funding

Department of Health BRC-1215-20014Department of Health RG65966
6 · The paper itself

Abstract

Despite significant progress in unraveling the genetic causes of neurodevelopmental disorders (NDDs), a substantial proportion of individuals with NDDs remain without a genetic diagnosis after microarray and/or exome sequencing. Here, we aimed to assess the power of short-read genome sequencing (GS), complemented with long-read GS, to identify causal variants in participants with NDD from the National Institute for Health and Care Research (NIHR) BioResource project. Short-read GS was conducted on 692 individuals (489 affected and 203 unaffected relatives) from 465 families. Additionally, long-read GS was performed on five affected individuals who had structural variants (SVs) in technically challenging regions, had complex SVs, or required distal variant phasing. Causal variants were identified in 36% of affected individuals (177/489), and a further 23% (112/489) had a variant of uncertain significance after multiple rounds of re-analysis. Among all reported variants, 88% (333/380) were coding nuclear SNVs or insertions and deletions (indels), and the remainder were SVs, non-coding variants, and mitochondrial variants. Furthermore, long-read GS facilitated the resolution of challenging SVs and invalidated variants of difficult interpretation from short-read GS. This study demonstrates the value of short-read GS, complemented with long-read GS, in investigating the genetic causes of NDDs. GS provides a comprehensive and unbiased method of identifying all types of variants throughout the nuclear and mitochondrial genomes in individuals with NDD.

Indexed as

Genome, HumanNeurodevelopmental DisordersBase SequenceChromosome MappingHumansINDEL Mutationlong-read sequencingneurodevelopmental disordersstructural variantswhole-genome sequencing

Identifiers

PMID37541188
PMCPMC10432178

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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.