ArticleNature communications2020
Functional annotation of rare structural variation in the human brain.
Open access · goldAbstract read
In one paragraph
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
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.
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.
Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Determinants of functional burden pleiotropy and gene dosage responses across human traits.Nature communications · 2026Article
- Convergent coexpression reveals shared biological mechanisms underlying common and rare variant risk in six neuropsychiatric disorders.Molecular psychiatry · 2026Article
- Global impact of germline structural variation on the cancer proteome.Nature communications · 2026Article
- Genetic and Cortical Cell-Type Liability Architecture of Autism.Research square · 2026Article
- Genetic and Cortical Cell-Type Liability Architecture of Autism.bioRxiv : the preprint server for biology · 2025Article
- Mirror effect of genomic deletions and duplications on cognitive ability across the human cerebral cortex.Research square · 2025Article
- Mirror effect of genomic deletions and duplications on cognitive ability across the human cerebral cortex.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic targeting of alternative splicing caused by a lethal noncoding structural variant in X-linked dystonia parkinsonism.medRxiv : the preprint server for health sciences · 2025Article
- Haplotype-resolved genome and pan-genome graphs reveal the impacts of structural variation on functional genome and feather colors in chickens.iMetaOmics · 2025Article
- Diversity and consequences of structural variation in the human genome.Nature reviews. Genetics · 2025Review
- Assessing the diagnostic impact of blood transcriptome profiling in a pediatric cohort previously assessed by genome sequencing.NPJ genomic medicine · 2025Article
- Global DNA methylation differences involving germline structural variation impact gene expression in pediatric brain tumors.Nature communications · 2025Article
- Systematic identification of disease-causing promoter and untranslated region variants in 8040 undiagnosed individuals with rare disease.Genome medicine · 2025Article
- Identifying deleterious noncoding variation through gain and loss of CTCF binding activity.American journal of human genetics · 2025Article
- Inter-chromosomal insertions at Xq27.1 associated with retinal dystrophy induce dysregulation of LINC00632 and CDR1as/ciRS-7.American journal of human genetics · 2025Article
- Copy number variants and the tangential expansion of the cerebral cortex.Nature communications · 2025Article
- Quantifying the regulatory potential of genetic variants via a hybrid sequence-oriented model with SVEN.Nature communications · 2024Article
- Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.bioRxiv : the preprint server for biology · 2024Article
- Importance of copy number variants in childhood apraxia of speech and other speech sound disorders.Communications biology · 2024Article
- The Role of Structural Variants in the Genetic Architecture of Parkinson's Disease.International journal of molecular sciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 15 institutions in 3 countries.
Lide Han *Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-0132-2656
Xuefang Zhao *Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (M.I.T.), Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-4036-9577
Mary Lauren BentonVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-5485-1041
Thaneer PerumalSage Bionetworks, Seattle, WA, USA.
Ryan L CollinsProgram in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (M.I.T.), Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1268-9995
Gabriel E HoffmanPamela Sklar Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-0957-0224
Jessica S JohnsonPamela Sklar Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Laura SloofmanPamela Sklar Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Harold Z WangProgram in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (M.I.T.), Cambridge, MA, USA.
Matthew R StoneProgram in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (M.I.T.), Cambridge, MA, USA.
CommonMind Consortium
Kristen J BrennandPamela Sklar Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-0993-5956
Harrison BrandProgram in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (M.I.T.), Cambridge, MA, USA.
Solveig K SiebertsSage Bionetworks, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-1033-0954
Stefano MarencoHuman Brain Collection Core, Intramural Research Program, NIMH, National Institutes of Health, Bethesda, MD, USA.
Mette A PetersSage Bionetworks, Seattle, WA, USA.
Barbara K LipskaHuman Brain Collection Core, Intramural Research Program, NIMH, National Institutes of Health, Bethesda, MD, USA.
Panos RoussosPamela Sklar Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-4640-6239
John A CapraVanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-9743-1795
Michael TalkowskiProgram in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (M.I.T.), Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2889-0992
Douglas M RuderferDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. douglas.ruderfer@vanderbilt.edu.ORCID http://orcid.org/0000-0002-2365-386X
Icahn School of Medicine at Mount Sinai · USBroad Institute · USAllen Institute for Brain Science · USNational Institutes of Health · USSage Bionetworks · USUniversity of Pittsburgh · USUniversity of Trento · ITDuke University · USNational Institute of Mental Health · USUniversity of Pennsylvania · USVanderbilt Health · USVanderbilt University Medical Center · USAarhus University · DKUniversity of North Carolina at Chapel Hill · USVanderbilt University · US
Funding
Procurement and Characterization of Postmortem Brain TissueZICMH002903 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MARENCO, STEFANO · 2009 to 2025
$56.0MVESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SEWELL, MARGARET · 1985 to 2019
$37.9MQUANTITATIVE ANALYSIS OF MICROVASCULAR CHANGES IN THE AGING BRAINP01AG002219 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HAROUTUNIAN, VAHRAM · 1985 to 2009
$19.2MWhite Matter Abnormalities in SchizophreniaP50MH066392 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BUXBAUM, JOSEPH D. · 2002 to 2012
$18.6MTraining Program in Bioinformatics and Integrative GenomicsT32HG002295 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Peter J Park · 2001 to 2026
$15.8MProject 5: In vivo measurement of GABA transmission in healthy controls & subjectP50MH084053 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEWIS, DAVID A · 2008 to 2012
$11.5MInternational Cohort Collection for Bipolar DisorderR01MH085542 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SMOLLER, JORDAN W · 2008 to 2012
$10.7MCis-Regulatory Epigenome Mappings in SchizophreniaU01MH103392 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, SKLAR, PAMELA · 2014 to 2017
$7.6MClinical Diagnostic Sequencing of Structural VariationR01HD081256 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2015 to 2025
$7.2MMolecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9MScalable tool and comprehensive maps to interpret structural variation across the neuropsychiatric spectrumR01MH115957 · NIMH · BROAD INSTITUTE, INC. · PI TALKOWSKI, MICHAEL E · 2019 to 2025
$5.4MGenetics Association in Schizophrenia and Other DisordersR37MH057881 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DEVLIN, BERNIE · 2013 to 2022
$5.4MIntramural NIH HHS Z01 MH002903Intramural NIH HHS ZIC MH002903NHGRI NIH HHS T32 HG002295NIA NIH HHS P01 AG002219NIA NIH HHS P50 AG005138NIA NIH HHS T32 AG049688NICHD NIH HHS R01 HD081256NICHD NIH HHS R01 HD096326NIDA NIH HHS HHSN271201300031CNIDA NIH HHS HHSN271201400099CNIGMS NIH HHS R35 GM127087NIH HHS S10 OD018522NIH HHS S10 OD026880NIMH NIH HHS P50 MH066392NIMH NIH HHS P50 MH084053NIMH NIH HHS R01 MH075916NIMH NIH HHS R01 MH080405NIMH NIH HHS R01 MH085542NIMH NIH HHS R01 MH093725NIMH NIH HHS R01 MH097276NIMH NIH HHS R01 MH109677NIMH NIH HHS R01 MH109897NIMH NIH HHS R01 MH110921NIMH NIH HHS R01 MH111776NIMH NIH HHS R01 MH115957NIMH NIH HHS R37 MH057881NIMH NIH HHS U01 MH103392NINDS NIH HHS L30 NS093200NINDS NIH HHS R01 NS093200NLM NIH HHS T32 LM012412
Abstract
Structural variants (SVs) contribute to many disorders, yet, functionally annotating them remains a major challenge. Here, we integrate SVs with RNA-sequencing from human post-mortem brains to quantify their dosage and regulatory effects. We show that genic and regulatory SVs exist at significantly lower frequencies than intergenic SVs. Functional impact of copy number variants (CNVs) stems from both the proportion of genic and regulatory content altered and loss-of-function intolerance of the gene. We train a linear model to predict expression effects of rare CNVs and use it to annotate regulatory disruption of CNVs from 14,891 independent genome-sequenced individuals. Pathogenic deletions implicated in neurodevelopmental disorders show significantly more extreme regulatory disruption scores and if rank ordered would be prioritized higher than using frequency or length alone. This work shows the deleteriousness of regulatory SVs, particularly those altering CTCF sites and provides a simple approach for functionally annotating the regulatory consequences of CNVs.
Indexed as
DNA Copy Number VariationsGene Expression RegulationGenetic VariationAutopsyBrainFemaleGene Expression ProfilingGenome, HumanHumansMaleNeurodevelopmental DisordersSequence Analysis, RNA
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
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.