Evidence map›Paper›PMID 42238450›Full record

ArticlemedRxiv : the preprint server for health sciences2026

The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.

Duncan S Palmer, Barney Hill, Sam Hodgson, Maarja Jõeloo, Georgios Kalantzis, Athanasios Kousathanas, Satoshi Koyama, Wenhan Lu, Shinichi Namba, Zachary B Rodriguez and 47 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

57 authors.

Duncan S PalmerBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.ORCID 0000-0002-0824-0047
Barney HillCentre for Human Genetics, University of Oxford, Oxford, UK.
Sam HodgsonWolfson Institute of Population Health, Queen Mary University of London, London, UK.
Maarja JõelooEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Georgios KalantzisWellcome Sanger Institute, Hinxton, UK.
Athanasios KousathanasGenomics England, London, UK.
Satoshi KoyamaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Wenhan LuProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Shinichi NambaDepartment of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Zachary B RodriguezDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jonathan A ShorttDepartment of Biomedical Informatics, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Kyuto SoneharaDepartment of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nicholas VartanianThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ha My T VyThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Isaac A WadeNuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, UK.
Samantha L WhiteDepartment of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA.
Nikolas A BayaBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
Nathalie ChamiThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ron DoThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Karol EstradaTranslational Genomics, Maze Therapeutics, South San Francisco, CA, USA.
Sarah FinerWolfson Institute of Population Health, Queen Mary University of London, London, UK.
Giulio GenoveseStanley Center, Broad Institute of MIT and Harvard, MA, USA.
Jeremy GuezProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yuval ItanThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Masahiro KanaiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Frederik H LassenBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
Koichi MatsudaLaboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Loukas MoutsianasGenomics England, London, UK.
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Priit PaltaEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Daniel J RaderDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Augusto RendonGenomics England, London, UK.
Ghislain RocheleauThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Omid Sadeghi-AlavijehCentre for Kidney and Bladder Health, University College London, London, UK.
Margaret Sunitha SelvarajCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Roelof Aj SmitThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Dapeng WangNational Heart and Lung Institute, Imperial College London, London, UK.
Emilie M WigdorInstitute of Developmental and Regenerative Medicine, University of Oxford, Oxford, UK.
Zhi YuCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Colorado Center for Personalized Medicine
Estonian Biobank Research Team
Genes & Health Industry Consortium
Genes & Health Research Team, Penn Medicine BioBank, The BioBank Japan Project
Christopher R GignouxDepartment of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA.
Henrike HeyneProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ruth Jf LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Hilary C MartinWellcome Sanger Institute, Hinxton, UK.
Lili MilaniEstonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Pradeep NatarajanProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yukinori OkadaDepartment of Genome Informatics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Nikita PozdeyevDepartment of Biomedical Informatics, University of Colorado Anschutz, Aurora, CO, USA.
David A van HeelBlizard Institute, Queen Mary University of London, 4 Newark Street, London, UK.
Anurag VermaDivision of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wei ZhouProgram 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.
Cecilia M LindgrenDepartment of Statistics, University of Oxford, Oxford, UK.
Benjamin M NealeProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Funding

The Massachusetts General Hospital Harvard Center for Reproductive MedicineP50HD104224 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI SEMINARA, STEPHANIE BETH · 2021 to 2025
$7.8M
An integrative approach to disease gene discovery combining genetic variation, gene expression, and epigenetics.R00HG012222 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI Wei Zhou · 2024 to 2026
$747k
Bill & Melinda Gates Foundation INV-024200NHGRI NIH HHS R00 HG012222NICHD NIH HHS P50 HD104224Wellcome Trust
6 · The paper itself

Abstract

Rare coding variants can have large effects on disease risk and provide direct routes from human genetics to disease mechanisms and therapeutic targets, but their discovery is constrained by sample size, particularly for low-prevalence diseases. Here we establish the Biobank Rare Variant Analysis (BRaVa) consortium, a global rare variant association resource that integrates sequencing and linked health-record data from ten biobanks and cohorts comprising over 1.2 million individuals across diverse ancestries. We performed gene-based meta-analyses of rare coding variation across 33 clinical endpoints and 11 quantitative traits. Aggregating evidence across biobanks and ancestries identified 514 gene-trait associations, including 31 not previously reported in prior studies or curated association resources following systematic literature review. Notably, 36.1% of gene-level associations were undetectable in any individual biobank, and 91 emerged only through cross-ancestry meta-analysis, demonstrating that federated integration enables discovery beyond the reach of single cohorts. Similar gains were observed at the variant level, where 25.0% of phenotype-locus associations were detectable only through meta-analysis. Effect size estimates were correlated across ancestries with concordant directions of effect, supporting the generalizability of rare variant associations. The identified signals implicate pathways involved in transcriptional and epigenetic regulation, metabolism, vascular and epithelial biology, and immune function, highlighting rare coding variation as an engine for biological discovery across medical record phenotypes. For example, damaging variation in

Identifiers

PMID42238450
PMCPMC13228758

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