ArticleNature methods2022
A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies.
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Article in Nature methods, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 3 of them syntheses that pooled it.
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80citing papers in PubMed, 3 pooled it
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Who cites it
80 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Whole genome sequence analysis of low-density lipoprotein cholesterol across 246 K individuals.Genome biology · 2025Pooled it
- Assessment of the functionality and usability of open-source rare variant analysis pipelines.Briefings in bioinformatics · 2025Pooled it
- Powerful, scalable and resource-efficient meta-analysis of rare variant associations in large whole genome sequencing studies.Nature genetics · 2023Pooled it
- Explaining the unexplained admixture mapping signals via rare variants: the HCHS/SOL.Human molecular genetics · 2026Article
- Robust Inference With Ghostknockoffs in Genome-Wide Association Studies With Sample Relatedness.Genetic epidemiology · 2026Article
- Genome-Wide Association Study and Genomic Selection for Average Daily Gain in Ashidan Yak.Animals : an open access journal from MDPI · 2026Article
- Identification of novel loci regulating circulating melatonin and its causal relationship with hypertension.Human genetics · 2026Article
- Atlas of glomerular disease-specific genetic effects on blood transcriptome.medRxiv : the preprint server for health sciences · 2026Article
- Whole-genome sequencing implicates rare, low-frequency and structural non-coding variation at themedRxiv : the preprint server for health sciences · 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
- Integrating common and rare variants improves polygenic risk prediction across diverse populations.Nature communications · 2026Article
- Application of the STAAR framework in detecting rare variant associations with Alzheimer disease and related dementias: Insights and implications.HGG advances · 2026Article
- Genome-wide detection of human 5' UTR variants that impact protein translation.American journal of human genetics · 2026Article
- Rare coding and noncoding variants map 1,342 diseases and biomarkers in 490,549 whole genomes.medRxiv : the preprint server for health sciences · 2026Article
- Elucidating genetic backgrounds of myasthenia gravis in Japanese by genome-wide association studies and multi-omics analyses of thymoma.Nature communications · 2026Article
- Scalable and accurate rare-variant association tests for whole genome sequencing time-to-event analysis in large biobanks.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- cellSTAAR: incorporating single-cell-sequencing-based functional data to boost power in rare variant association testing of noncoding regions.Nature methods · 2026Article
- Archipelago Method for Variant Set Association Test Statistics.Genetic epidemiology · 2026Article
- Genetic Architecture of N-Terminal Pro-B-Type Natriuretic Peptide in a Multiancestry Study Population.Circulation. Genomic and precision medicine · 2026Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
70 authors.
Zilin Li *Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. li@hsph.harvard.edu.ORCID http://orcid.org/0000-0003-1521-8945
Xihao Li *Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8151-0106
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.
Margaret Sunitha SelvarajCenter for Genomic Medicine and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-2751-9254
Theodore ArapoglouDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Corbin QuickDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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.
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.
Donna K ArnettDean's Office, University of Kentucky, College of Public Health, Lexington, KY, USA.
Paul L AuerDivision of Biostatistics, Institute for Health & Equity and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Lawrence F BielakDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3443-8030
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Thomas W BlackwellDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, 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.
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 http://orcid.org/0000-0001-8509-148X
Brian E CadeProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Matthew P ConomosDepartment of Biostatistics, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-9744-0851
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.
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 http://orcid.org/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.
Nora FranceschiniDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Barry I FreedmanDepartment of Internal Medicine, Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.ORCID http://orcid.org/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 http://orcid.org/0000-0002-5264-5068
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 http://orcid.org/0000-0002-7986-8560
Brian G KralGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Leslie A LangeDivision of Biomedical Informatics and Personalized Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Bridget M LinDepartment of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
Ani ManichaikulCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
Alisa K ManningDepartment of Medicine, Harvard Medical School, Boston, MA, USA.
Lisa W MartinDivision in Cardiology, George Washington School of Medicine and Health Sciences, Washington, DC, USA.
Rasika A MathiasGeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
James B MeigsProgram in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
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.
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.
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 http://orcid.org/0000-0001-8883-2511
Patricia A PeyserDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9717-8459
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
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 http://orcid.org/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 http://orcid.org/0000-0002-3071-7278
Stephen S RichCenter for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.ORCID http://orcid.org/0000-0003-3872-7793
Jennifer A SmithDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/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.
Margaret A TaubDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Ramachandran S VasanFramingham Heart Study, National Heart, Lung, and Blood Institute and Boston University, Framingham, MA, USA.ORCID http://orcid.org/0000-0001-7357-5970
Daniel E WeeksDepartment of Human Genetics and Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-9410-7228
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 http://orcid.org/0000-0001-7117-1075
Wei ZhaoDepartment of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
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.
Cristen J WillerDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-5645-4966
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 http://orcid.org/0000-0002-5355-8636
Xihong LinDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. xlin@hsph.harvard.edu.ORCID http://orcid.org/0000-0001-7067-7752
Funding
Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1MLarge Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8MStatistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6MUCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MClinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0MUniversity of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MUnderstanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRESCOTT G WOODRUFF · 2008 to 2026
$41.1MPulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
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Abstract
Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust noncoding RV association detection framework, STAARpipeline, to automatically annotate a whole-genome sequencing study and perform flexible noncoding RV association analysis, including gene-centric analysis and fixed window-based and dynamic window-based non-gene-centric analysis by incorporating variant functional annotations. In gene-centric analysis, STAARpipeline uses STAAR to group noncoding variants based on functional categories of genes and incorporate multiple functional annotations. In non-gene-centric analysis, STAARpipeline uses SCANG-STAAR to incorporate dynamic window sizes and multiple functional annotations. We apply STAARpipeline to identify noncoding RV sets associated with four lipid traits in 21,015 discovery samples from the Trans-Omics for Precision Medicine (TOPMed) program and replicate several of them in an additional 9,123 TOPMed samples. We also analyze five non-lipid TOPMed traits.
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GenomeGenome-Wide Association StudyGenetic VariationHumansPhenotypeWhole Genome Sequencing
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