Evidence map›Paper›PMID 35168652›Full record

ArticleGenome biology2022

Placental methylome reveals a 22q13.33 brain regulatory gene locus associated with autism.

Yihui Zhu, J Antonio Gomez, Benjamin I Laufer, Charles E Mordaunt, Julia S Mouat, Daniela C Soto, Megan Y Dennis, Kelly S Benke, Kelly M Bakulski, John Dou and 15 more

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

Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
6.0field-weighted citation impact, top 2% 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

38 citing papers in PubMed, 65 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. A comprehensive guide to genomeZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Review
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  6. Review
  7. Article
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  10. Article
  11. Review
  12. Article
  13. Placental biomarkers for the prediction of neurodevelopmental disorders.Frontiers in cell and developmental biology · 2025
    Review
  14. Article
  15. Expanding Upon Genomics in Rare Diseases: Epigenomic Insights.International journal of molecular sciences · 2024
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review
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

25 authors at 6 institutions in 2 countries.

Yihui ZhuDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
J Antonio GomezDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Benjamin I LauferDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Charles E MordauntDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Julia S MouatDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Daniela C SotoGenome Center, University of California, Davis, CA, USA.
Megan Y DennisGenome Center, University of California, Davis, CA, USA.
Kelly S BenkeDepartment of Public Health Sciences, University of California, Davis, CA, USA.
Kelly M BakulskiDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
John DouDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Ria MaratheDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Julia M JianuDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Logan A WilliamsDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Orangel J Gutierrez FugónDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Cheryl K WalkerPerinatal Origins of Disparities Center, University of California, Davis, CA, USA.
Sally OzonoffMIND Institute, School of Medicine, University of California, Davis, CA, USA.
Jason DanielsDepartment of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Luke P GrosvenorDepartment of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Heather E VolkDepartment of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Jason I FeinbergWendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
M Daniele FallinWendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Irva Hertz-PicciottoPerinatal Origins of Disparities Center, University of California, Davis, CA, USA.
Rebecca J SchmidtPerinatal Origins of Disparities Center, University of California, Davis, CA, USA.
Dag H YasuiDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA.
Janine M LaSalleDepartment of Medical Microbiology and Immunology, University of California, Davis, CA, USA. jmlasalle@ucdavis.edu.ORCID 0000-0002-3480-2031
University of California Davis Medical Center · USUniversity of California, Davis · USJohns Hopkins University · USUniversity of Michigan · USInstitute of Behavioral Sciences · JPUniversity of California System · US

Funding

UC Davis Environmental Health Sciences Core CenterP30ES023513 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Ameer Taha · 2015 to 2026
$26.0M
Revisiting ReCHARGE: ECHO Follow up on Middle Childhood and AdolescenceUH3OD023365 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Deborah Hall Bennett, Irva Hertz-Picciotto · 2018 to 2026
$21.9M
Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3M
UC Davis Center for Children's Environmental Health (CCEH)P01ES011269 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI VAN DE WATER, JUDY A. · 2001 to 2018
$12.5M
Research Project: Pathologic Significance of Maternal AutoantibodiesP50HD103526 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEONARD J. ABBEDUTO, Melissa Dawn Bauman · 2020 to 2026
$9.7M
Autism Risk, Prenatal Environmental Exposures, and Pathophysiologic MarkersR01ES020392 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI HERTZ-PICCIOTTO, IRVA, OZONOFF, SALLY · 2011 to 2015
$9.0M
Rodent Behavior CoreU54HD079125 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI OZONOFF, SALLY · 2013 to 2019
$8.5M
PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES)R01ES029213 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Janine M LaSalle, Pamela J Lein · 2018 to 2026
$6.5M
Folic Acid Prevention Pathways for ASD in High Risk FamiliesR01ES025574 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI SCHMIDT, REBECCA JEAN · 2015 to 2019
$3.1M
The function of duplicated genes in human brain evolution and diseaseDP2MH119424 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DENNIS, MEGAN Y · 2018 to 2018
$2.4M
BUILDS MARBLES: Biorepository Upkeep and Infrastructure for Longitudinal Data Sharing for MARBLESR24ES028533 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Brittany D. Chambers Butcher, Rebecca Jean Schmidt · 2017 to 2026
$2.3M
BUILDS MARBLES: Biorepository Upkeep and Infrastructure for Longitudinal Data Sharing for MARBLESU24ES028533 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CHAMBERS BUTCHER, BRITTANY D., SCHMIDT, REBECCA JEAN · 2023 to 2025
$1.2M
NICHD NIH HHS P50 HD103526NICHD NIH HHS U54 HD079125NIEHS NIH HHS P01 ES011269NIEHS NIH HHS P30 ES017885NIEHS NIH HHS P30 ES023513NIEHS NIH HHS R01 ES020392NIEHS NIH HHS R01 ES025574NIEHS NIH HHS R01 ES029213NIEHS NIH HHS R24 ES028533NIEHS NIH HHS U24 ES028533NIH HHS UH3 OD023365NIMH NIH HHS DP2 MH119424
6 · The paper itself

Abstract

backgroundAutism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome.

resultsWe use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence.

conclusionsTogether, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.

Indexed as

Autism Spectrum DisorderAutistic DisorderBrainDNA MethylationEpigenesis, GeneticEpigenomeFemaleGenes, RegulatorHumansInfant, NewbornPlacentaPregnancyProspective StudiesAutism spectrum disorderDNA methylationEpigenomicsHuman geneticsHypoxiaNeurodevelopmentPlacentaPostmortem brainProspective studyStructural variants

Identifiers

PMID35168652
PMCPMC8848662
OpenAlexW4213130520

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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.