Evidence map›Paper›PMID 31873310›Full record

ArticleNature medicine2020

Autism risk in offspring can be assessed through quantification of male sperm mosaicism.

Martin W Breuss, Danny Antaki, Renee D George, Morgan Kleiber, Kiely N James, Laurel L Ball, Oanh Hong, Ileena Mitra, Xiaoxu Yang, Sara A Wirth and 20 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
24.4field-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

63 citing papers in PubMed, 106 citations in OpenAlex.

  1. Trial
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  10. Age-related changes in lncRNA expression in sperm.Translational andrology and urology · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. [Sperm Mosaic Variants and Their Influence on the Offspring].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024
    Review
  17. Article
  18. Article
  19. Article
  20. Parental age effects and Rett syndrome.American journal of medical genetics. Part A · 2024
    Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 6 institutions in 2 countries.

Martin W BreussDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Danny AntakiBeyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
Renee D GeorgeDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Morgan KleiberBeyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
Kiely N JamesDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Laurel L BallDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Oanh HongBeyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
Ileena MitraDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Xiaoxu YangDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0219-0023
Sara A WirthDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Jing GuDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Camila A B GarciaDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Madhusudan GujralBeyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
William M BrandlerBeyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA.
Damir MusaevDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
An NguyenDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Jennifer McEvoy-VenneriDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Renatta KnoxDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Evan SticcaDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA.
Martha Cristina Cancino BotelloChild and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Barcelona, Spain.
Javiera Uribe FennerChild and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Barcelona, Spain.
Maria Cárcel PérezFundació Docència i Recerca Mútua Terrassa, Barcelona, Spain.
Maria ArranzFundació Docència i Recerca Mútua Terrassa, Barcelona, Spain.
Andrea B MoffittCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Zihua WangCold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY, USA.
Amaia HervásResearch Laboratory Unit, Fundació Docencia i Recerca Mútua Terrassa, Barcelona, Spain.
Orrin DevinskyDepartment of Neurology, Epilepsy Division, New York University School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-0044-4632
Melissa GymrekDepartment of Medicine, University of California, San Diego, La Jolla, CA, USA.
Jonathan SebatBeyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA, USA. jsebat@ucsd.edu.ORCID http://orcid.org/0000-0002-9087-526X
Joseph G GleesonDepartment of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA, USA. jogleeson@ucsd.edu.ORCID http://orcid.org/0000-0002-0889-9220
Children’s Institute · USUniversity of California San Diego · USUniversity Hospital Mútua de Terrassa · ESCold Spring Harbor Laboratory · USMútua Terrassa · ESNew York University · US

Funding

U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Project II - Modeling meningomyelocele in frog using human alleles and folic acid exposureP01HD104436 · NICHD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2021 to 2025
$7.0M
The Role of Germline Mutation and Parental Age in Autism Spectrum DisordersR01MH076431 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEBAT, JONATHAN · 2005 to 2015
$5.5M
Mosaicism in focal cortical dysplasias spectrum seen in neuropsychiatric diseaseU01MH108898 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2015 to 2019
$5.1M
Expanding the accessible genetic architecture of autism by single molecule sequencingR01MH113715 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEBAT, JONATHAN · 2017 to 2021
$4.1M
Molecular characterization of HemimegalencephalyR01NS083823 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, MATHERN, GARY W. · 2013 to 2017
$3.1M
Burden of brain somatic mosaicism in Alzheimer's diseaseR21AG070462 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2020 to 2020
$434k
Austrian Science Fund FWF J 4197Medical Research Council G90/100NIA NIH HHS R21 AG070462NICHD NIH HHS P01 HD104436NIMH NIH HHS R01 MH076431NIMH NIH HHS R01 MH113715NIMH NIH HHS U01 MH108898NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS083823
6 · The paper itself

Abstract

De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recurrence and a small fraction with a substantially higher and quantifiable risk, and we identify novel mosaic variants at risk for transmission to a future offspring. This suggests, therefore, that genetic counseling would benefit from the addition of sperm mosaicism assessment.

Indexed as

Genetic Predisposition to DiseaseMosaicismAutistic DisorderFemaleHumansMaleMutationPedigreePolymorphism, Single NucleotideRecurrenceRisk FactorsSpermatozoa

Identifiers

PMID31873310
PMCPMC7032648
OpenAlexW2996077740

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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.