ArticleNature2024
A genomic mutational constraint map using variation in 76,156 human genomes.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1,145 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
1,145citing papers in PubMed, 1 pooled it
373.2field-weighted citation impact, top 1% 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
1,145 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,193 citations in OpenAlex.
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- A Novel Homozygous Variant Associated With Distinct Clinical Phenotypes of SDR9C7 Nonsyndromic Epidermal Differentiation Disorder in Two Affected Patients From a Consanguineous Saudi Family.Molecular genetics & genomic medicine · 2026Article
- Tofersen treatment in respiratory onset amyotrophic lateral sclerosis and a variant of uncertain significance in SOD1; a case report.European journal of human genetics : EJHG · 2026Article
- An Icelandic pangenome reference.Nature · 2026Article
- SPLENDID incorporates continuous genetic ancestry in biobank-scale data to improve polygenic risk prediction across diverse populations.Nature methods · 2026Article
- From Pathogenicity to Mechanism: A Variant Interpretation Framework for Monogenic Epilepsy.Clinical genetics · 2026Article
- The global burden of metabolic and alcohol-associated liver disease (MetALD).Hepatology communications · 2026Review
1,085 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
47 authors at 20 institutions in 24 countries.
Siwei Chen *Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. siwei@broadinstitute.org.
Laurent C Francioli *Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Julia K GoodrichProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ryan L CollinsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Masahiro KanaiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-5165-4408
Qingbo WangProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-9110-5830
Jessica AlföldiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-9713-6200
Nicholas A WattsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Christopher VittalProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Laura D GauthierData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Timothy PoterbaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Michael W WilsonProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yekaterina TarasovaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
William PhuProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-5569-1000
Riley GrantProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Mary T YohannesProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zan KoenigAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Yossi FarjounRichards Lab, Lady Davis Institute, Montreal, Quebec, Canada.ORCID 0000-0002-7002-2868
Eric BanksData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stacey DonnellyBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Stacey GabrielBroad Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Namrata GuptaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Steven FerrieraBroad Genomics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Charlotte TolonenData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sam NovodData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Louis BergelsonData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
David RoazenData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Valentin Ruano-RubioData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Miguel CovarrubiasData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Christopher LlanwarneData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nikelle PetrilloData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Gordon WadeData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Thibault JeandetData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ruchi MunshiData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Kathleen TibbettsData Science Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Genome Aggregation Database Consortium
Anne O'Donnell-LuriaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-6418-9592
Matthew SolomonsonProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cotton SeedAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Alicia R MartinProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-0241-3522
Michael E TalkowskiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Heidi L RehmProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-6025-0015
Mark J DalyProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-0949-8752
Grace TiaoProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Benjamin M Neale *Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0003-1513-6077
Daniel G MacArthur *Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Konrad J KarczewskiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. konradk@broadinstitute.org.ORCID 0000-0003-2878-4671
Broad Institute · USUniversity of Helsinki · FIHarvard University · USBrigham and Women's Hospital · USCardiff University · GBFinnish Institute for Health and Welfare · FIHelsinki University Hospital · FIIcahn School of Medicine at Mount Sinai · USInstituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán · MXUniversity of Eastern Finland · FIBoston University · USChinese University of Hong Kong · HKColumbia University Irving Medical Center · USHebrew University of Jerusalem · ILImperial College Healthcare NHS Trust · GBJohns Hopkins University · USKorea National Institute of Health · KRNational University of Singapore · SGTampere University of Applied Sciences · FIUCLA Medical Center · US
Funding
The Genome Aggregation Database (gnomAD)U24HG011450 · NHGRI · BROAD INSTITUTE, INC. · PI Mark Joseph Daly, Konrad Karczewski · 2021 to 2026
$22.3MComputational resources for genomic interpretation of type 2 diabetesU54DK105566 · NIDDK · BROAD INSTITUTE, INC. · PI MACARTHUR, DANIEL G, NEALE, BENJAMIN MICHAEL · 2014 to 2017
$8.6MClinical Diagnostic Sequencing of Structural VariationR01HD081256 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2015 to 2025
$7.2MScalable tool and comprehensive maps to interpret structural variation across the neuropsychiatric spectrumR01MH115957 · NIMH · BROAD INSTITUTE, INC. · PI TALKOWSKI, MICHAEL E · 2019 to 2025
$5.4MMedical Research Council MC_UP_1102/20NHGRI NIH HHS U24 HG011450NICHD NIH HHS R01 HD081256NIDDK NIH HHS U54 DK105566NIMH NIH HHS R01 MH115957
Abstract
The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders
Indexed as
Genome, HumanGenomicsModels, GeneticMutationAccess to InformationDatabases, GeneticDatasets as TopicGene FrequencyHumansSelection, Genetic
Identifiers
What OpenQuestion holds
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Read underepoch 390
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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.