Evidence mapPaperPMID 41266648Full record

SynthesisNature genetics2025

Scalable and accurate rare variant meta-analysis with Meta-SAIGE.

Eunjae Park, Kisung Nam, Seokho Jeong, Karl Keat, Dokyoon Kim, Vikas Bansal, Wei Zhou, Seunggeun Lee

Abstract readMeta-Analysis
In one paragraph

Synthesis in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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5 · Who and what money

Authors and funding

8 authors.

Eunjae Park *Graduate School of Data Science, Seoul National University, Seoul, Republic of Korea.
Kisung Nam *Graduate School of Data Science, Seoul National University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0002-7317-092X
Seokho Jeong *Graduate School of Data Science, Seoul National University, Seoul, Republic of Korea.
Karl KeatDepartment of Genetics, University of Pennsylvania, Pennsylvania, PA, USA.ORCID http://orcid.org/0000-0002-0945-5816
Dokyoon KimDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA.ORCID http://orcid.org/0000-0002-4592-9564
Vikas BansalDepartment of Pediatrics, School of Medicine, University of California, La Jolla, San Diego, CA, USA.
Wei ZhouPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Boston, MA, USA. wzhou@broadinstitute.org.ORCID http://orcid.org/0000-0001-7719-0859
Seunggeun LeeGraduate School of Data Science, Seoul National University, Seoul, Republic of Korea. lee7801@snu.ac.kr.ORCID http://orcid.org/0000-0002-8097-3878

Funding

An integrative approach to disease gene discovery combining genetic variation, gene expression, and epigenetics.R00HG012222 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$249k
Augmenting Pharmacogenetics with Multi-Omics Data and Techniques to Predict Adverse Drug Reactions to NSAIDsF31HG013246 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$49k
Ministry of Food and Drug Safety (MFDS) 23212MFDS202National Research Foundation of Korea (NRF) 2020H1D3A2A03100666NHGRI NIH HHS F31 HG013246NHGRI NIH HHS R00 HG012222U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R00HG012222
6 · The paper itself

Abstract

Meta-analysis enhances the power of rare variant association tests by combining summary statistics across several cohorts. However, existing methods often fail to control type I error for low-prevalence binary traits and are computationally intensive. Here we introduce Meta-SAIGE-a scalable method for rare variant meta-analysis that accurately estimates the null distribution to control type I error and reuses the linkage disequilibrium matrix across phenotypes to boost computational efficiency in phenome-wide analyses. Simulations using UK Biobank whole-exome sequencing data show that Meta-SAIGE effectively controls type I error and achieves power comparable to pooled individual-level analysis with SAIGE-GENE+. Applying Meta-SAIGE to 83 low-prevalence phenotypes in UK Biobank and All of Us whole-exome sequencing data identified 237 gene-trait associations. Notably, 80 of these associations were not significant in either dataset alone, underscoring the power of our meta-analysis.

Indexed as

Genetic VariationMeta-Analysis as TopicComputer SimulationExome SequencingGenome-Wide Association StudyHumansLinkage DisequilibriumModels, GeneticPhenotypePolymorphism, Single Nucleotide

Identifiers

PMID41266648
PMCPMC12695641

What Socratic holds

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Registered trials

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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 Socratic graph.