Evidence map›Paper›PMID 36778668›Full record

ArticleCell genomics2022

Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes.

Konrad J Karczewski, Matthew Solomonson, Katherine R Chao, Julia K Goodrich, Grace Tiao, Wenhan Lu, Bridget M Riley-Gillis, Ellen A Tsai, Hye In Kim, Xiuwen Zheng and 35 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
212citing papers in PubMed, 7 pooled it
–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

212 citing papers in PubMed, 7 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Pooled it
  4. Diagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Guideline
  5. Pooled it
  6. Pooled it
  7. A stop-gain variant inHGG advances · 2023
    Pooled it
  8. Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    Trial
  9. Article
  10. OPA1 controls mitochondrial dysfunction-driven liver fibrosis in MASLD.bioRxiv : the preprint server for biology · 2026
    Article
  11. Article
  12. AlphaGenome Atlas:medRxiv : the preprint server for health sciences · 2026
    Article
  13. The GPCRDiabetologia · 2026
    Article
  14. Article
  15. Glycemic and bodyweight effects ofScience advances · 2026
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

45 authors.

Konrad J KarczewskiProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Matthew SolomonsonProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Katherine R ChaoProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Julia K GoodrichProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Grace TiaoProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Wenhan LuProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bridget M Riley-GillisGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
Ellen A TsaiBiogen, Inc., Cambridge, MA 02142, USA.
Hye In KimWorldwide Research Development and Medical, Pfizer, Inc., Cambridge, MA 02139, USA.
Xiuwen ZhengGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
Fedik RahimovGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
Sahar EsmaeeliGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
A Jason GrundstadGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
Mark ReppellGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
Jeff WaringGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
Howard JacobGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
David SextonBiogen, Inc., Cambridge, MA 02142, USA.
Paola G BronsonBiogen, Inc., Cambridge, MA 02142, USA.
Xing ChenWorldwide Research Development and Medical, Pfizer, Inc., Cambridge, MA 02139, USA.
Xinli HuWorldwide Research Development and Medical, Pfizer, Inc., Cambridge, MA 02139, USA.
Jacqueline I GoldsteinProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel KingProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christopher VittalProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Timothy PoterbaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Duncan S PalmerProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Claire ChurchhouseProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel P HowriganProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Wei ZhouProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nicholas A WattsProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kevin NguyenProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Huy NguyenProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cara MasonData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christopher FarnhamData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Charlotte TolonenData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Laura D GauthierData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Namrata GuptaData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel G MacArthurProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Heidi L RehmProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Cotton SeedProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Anthony A PhilippakisData Sciences Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mark J DalyProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
J Wade DavisGenomics Research Center, AbbVie, North Chicago, IL 60064, USA.
Heiko RunzBiogen, Inc., Cambridge, MA 02142, USA.
Melissa R MillerWorldwide Research Development and Medical, Pfizer, Inc., Cambridge, MA 02139, USA.
Benjamin M NealeProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Funding

Cell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1M
NIDDK NIH HHS R01 DK075787
6 · The paper itself

Abstract

Genome-wide association studies have successfully discovered thousands of common variants associated with human diseases and traits, but the landscape of rare variations in human disease has not been explored at scale. Exome-sequencing studies of population biobanks provide an opportunity to systematically evaluate the impact of rare coding variations across a wide range of phenotypes to discover genes and allelic series relevant to human health and disease. Here, we present results from systematic association analyses of 4,529 phenotypes using single-variant and gene tests of 394,841 individuals in the UK Biobank with exome-sequence data. We find that the discovery of genetic associations is tightly linked to frequency and is correlated with metrics of deleteriousness and natural selection. We highlight biological findings elucidated by these data and release the dataset as a public resource alongside the Genebass browser for rapidly exploring rare-variant association results.

Indexed as

biobanksexome sequencingGWASPheWASrare variant association studiesrare variants

Identifiers

PMID36778668
PMCPMC9903662

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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.