SynthesisNature genetics2023
Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 5 pooled it
–field-weighted citation impact
What it found
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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.
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Who cites it
46 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Genome-wide analysis implicates inner ear development in Ménière disease.American journal of human genetics · 2026Pooled it
- Computationally efficient meta-analysis of gene-based tests using summary statistics in large-scale genetic studies.Nature genetics · 2025Pooled it
- Scalable and accurate rare variant meta-analysis with Meta-SAIGE.Nature genetics · 2025Pooled it
- Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.Genome biology · 2025Pooled it
- Re-analysis and meta-analysis of summary statistics from gene-environment interaction studies.Bioinformatics (Oxford, England) · 2023Pooled it
- Robust Inference With Ghostknockoffs in Genome-Wide Association Studies With Sample Relatedness.Genetic epidemiology · 2026Article
- Isolation, Biocontrol Efficacy and Genomic Analysis ofMicroorganisms · 2026Article
- Article
- NERINE reveals rare variant associations in gene networks across phenotypes and implicates an SNCA-PRL-LRRK2 subnetwork in Parkinson's disease.Cell genomics · 2026Article
- MetaSTAARlite: an all-in-one tool for biobank-scale whole-genome sequencing meta-analysis.Nature computational science · 2026Article
- Whole genome sequencing analysis of over 3500 individuals dementia-free over 85 years old.Journal of Alzheimer's disease : JAD · 2026Article
- The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.medRxiv : the preprint server for health sciences · 2026Article
- Large scale wheat data integration improves genomic prediction accuracy with the potential to facilitate international breeding collaborations.Communications biology · 2026Article
- Integrating common and rare variants improves polygenic risk prediction across diverse populations.Nature communications · 2026Article
- Genomic signature driving preinvasive to invasive processes in stage I lung adenocarcinoma.International journal of cancer · 2026Article
- Integrated single marker scanning and sparse Bayesian learning improves performance of detection for GWAS.Plant methods · 2026Article
- Genome-wide analysis implicates inner ear development in Ménière's disease.medRxiv : the preprint server for health sciences · 2026Article
- Archipelago Method for Variant Set Association Test Statistics.Genetic epidemiology · 2026Article
- The era of "Infectious Diseases+" has arrived: multi-disciplinary integration in pediatric infectious disease prevention and control.Frontiers in pediatrics · 2026Review
- A scalable framework for identifying allelic series from summary statistics.American journal of human genetics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
61 authors.
Xihao LiDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-8151-0106
Corbin QuickDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0001-7199-2930
Hufeng ZhouDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Sheila M GaynorDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-7869-5223
Yaowu LiuSchool of Statistics, Southwestern University of Finance and Economics, Chengdu, China.
Han ChenHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Margaret Sunitha SelvarajCenter for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-2751-9254
Ryan SunDepartment of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rounak DeyDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID 0000-0002-6540-8280
Donna K ArnettUniversity of Kentucky, College of Public Health, Lexington, KY, USA.ORCID 0000-0003-2219-657X
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3443-8030
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
John BlangeroDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA.ORCID 0000-0001-6250-5723
Eric BoerwinkleHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Donald W BowdenDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0001-8509-148X
Brian E CadeProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0003-1424-0673
Adolfo CorreaJackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
L Adrienne CupplesDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID 0000-0003-0273-7965
Joanne E CurranDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA.ORCID 0000-0002-6898-155X
Paul S de VriesHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Ravindranath DuggiralaDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA.
Barry I FreedmanDepartment of Internal Medicine, Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.ORCID 0000-0003-0275-5530
Harald H H GöringDepartment of Human Genetics and South Texas Diabetes and Obesity Institute, School of Medicine, The University of Texas Rio Grande Valley, Brownsville, TX, USA.
Xiuqing GuoThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0002-5264-5068
Jeffrey HaesslerDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Rita R KalyaniGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID 0000-0002-7986-8560
Brian G KralGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-9493-2084
Leslie A LangeDivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Lisa W MartinDivision of Cardiology, George Washington School of Medicine and Health Sciences, Washington, DC, USA.ORCID 0000-0003-4352-0914
Stephen T McGarveyDepartment of Epidemiology, International Health Institute, Department of Anthropology, Brown University, Providence, RI, USA.ORCID 0000-0003-1233-6970
Braxton D MitchellDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
May E MontasserDivision of Endocrinology, Diabetes, and Nutrition, Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-9558-5456
Alanna C MorrisonHuman Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.ORCID 0000-0001-6381-4296
Take NaseriMinistry of Health, Government of Samoa, Apia, Samoa.
Jeffrey R O'ConnellDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Nicholette D PalmerDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.ORCID 0000-0001-8883-2511
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Susan RedlineDivision of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, USA.
Alexander P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID 0000-0002-1427-4470
Muagututi'a Sefuiva ReupenaLutia I Puava Ae Mapu I Fagalele, Apia, Samoa.
Kenneth M RiceDepartment of Biostatistics, University of Washington, Seattle, WA, USA.ORCID 0000-0002-3071-7278
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0003-3872-7793
Colleen M SitlaniCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3575-5468
Kent D TaylorThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Ramachandran S VasanFramingham Heart Study, National Heart, Lung, and Blood Institute and Boston University, Framingham, MA, USA.ORCID 0000-0001-7357-5970
Cristen J WillerDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-5645-4966
James G WilsonDivision of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Lisa R YanekGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-7117-1075
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-7388-0692
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Lipids Working Group
Jerome I RotterThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Pradeep NatarajanCenter for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Gina M PelosoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID 0000-0002-5355-8636
Zilin LiDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. li@hsph.harvard.edu.ORCID 0000-0003-1521-8945
Xihong LinDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. xlin@hsph.harvard.edu.ORCID 0000-0001-7067-7752
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrea L Hevener · 2003 to 2026
$40.4MZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI MARSH, LAURA · 1985 to 2007
$37.3MUNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3MWORKER PROTECTION AGAINST AIRBORNE INFLUENZA - A PILOT STUDYM01RR007122 · NCRR · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI KOCH, KENNETH L · 1992 to 2010
$35.2MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MFRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8MPEDIGREE ANALYSIS OF LIPOPROTEIN PHENOTYPESP01HL045522 · NHLBI · TEXAS BIOMEDICAL RESEARCH INSTITUTE · PI BLANGERO, JOHN · 1991 to 2012
$27.6MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MTranslating Molecular and Clinical Data to Population Lung Cancer Risk AssessmentU19CA203654 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Christopher I. Amos · 2017 to 2026
$23.7MIDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
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Abstract
Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a powerful and resource-efficient rare variant meta-analysis framework for large-scale WGS/WES studies. MetaSTAAR accounts for relatedness and population structure, can analyze both quantitative and dichotomous traits and boosts the power of rare variant tests by incorporating multiple variant functional annotations. Through meta-analysis of four lipid traits in 30,138 ancestrally diverse samples from 14 studies of the Trans Omics for Precision Medicine (TOPMed) Program, we show that MetaSTAAR performs rare variant meta-analysis at scale and produces results comparable to using pooled data. Additionally, we identified several conditionally significant rare variant associations with lipid traits. We further demonstrate that MetaSTAAR is scalable to biobank-scale cohorts through meta-analysis of TOPMed WGS data and UK Biobank WES data of ~200,000 samples.
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Genome-Wide Association StudyLipidsExome SequencingPhenotypeWhole Genome SequencingLipids
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