ArticleNature genetics2023
Adjusting for common variant polygenic scores improves yield in rare variant association analyses.
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Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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39citing papers in PubMed, 2 pooled it
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Empirically determined baseline masking strategies and other considerations for gene-level burden tests.Nature genetics · 2026Pooled it
- Boosting the power of genome-wide association studies within and across ancestries by using polygenic scores.Nature genetics · 2023Pooled it
- Polygenic risk scores in human genetics for study design discovery and translation.Human genetics · 2026Review
- Transcript-aware rare genetic variant association analyses of cardiopulmonary traits in participants from the All of Us Research Program.Nature communications · 2026Article
- Individuals who deviate from polygenic expectation are enriched for damaging variants in genes linked to rare disease.American journal of human genetics · 2026Article
- Diverse mediators of cancer predisposition uncovered by germline whole genome sequencing of unexplained familial cancers.medRxiv : the preprint server for health sciences · 2026Article
- Rare coding variant architecture and gene discovery from 130,000 sequenced cases of atrial fibrillation.Research square · 2026Article
- Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes.Diabetologia · 2026Article
- TBL1X/TBL1XR1 govern β-cell identity through a PAX6-containing gene regulatory network.Nature communications · 2026Article
- Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- Leveraging the shared and opposing genetic mechanisms in the heritable cardiomyopathies.Research square · 2026Article
- Multitrait analyses identify genetic variants associated with aortic valve function and aortic stenosis risk.Nature genetics · 2026Article
- Individuals whose phenotype deviates from genetic expectation defined by common variation are enriched for rare damaging variants in genes that cause rare disease.medRxiv : the preprint server for health sciences · 2025Article
- Genome-Wide Association Study of Hypoglycemia in Adults With Diabetes in the Million Veteran Program.Diabetes · 2025Article
- Common and rare genetic variants explain distinct diagnostic variance in pediatric attention deficit hyperactivity disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Improving type 2 diabetes polygenic risk scores by incorporating rare, low-frequency, and population-specific variants.medRxiv : the preprint server for health sciences · 2025Article
- Functional Role of Single-Nucleotide Polymorphisms on IFNG and IFNGR1 in Humans with Cardiovascular Disease.International journal of molecular sciences · 2025Article
- HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes.Cell metabolism · 2025Article
- Coagulation factor XII haploinsufficiency is protective against venous thromboembolism in a population-scale multidimensional analysis.Nature communications · 2025Article
- Metabolomics profiling in multi-ancestral individuals with type 2 diabetes in Singapore identified metabolites associated with renal function decline.Diabetologia · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Sean J Jurgens *Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1605-9782
James P Pirruccello *Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Seung Hoan ChoiCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2797-3190
Valerie N MorrillCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Mark ChaffinCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1234-5562
Steven A LubitzCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9599-4866
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9268-810X
Patrick T EllinorCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA. ellinor@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-2067-0533
Funding
IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6MTherapeutic target discovery in ADSP data via comprehensive whole-genome analysis incorporating ethnic diversity and systems approachesU01AG058589 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BOERWINKLE, ERIC A., DE JAGER, PHILIP L · 2018 to 2022
$11.1MUsing genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3MInterstitial Lung Abnormalities: Defining the Phenotype, Causes, and Consequences.R01HL111024 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HUNNINGHAKE, GARY MATTHEW · 2013 to 2022
$6.4MGenomics of Cardiac ArrhythmiasR01HL139731 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2018 to 2022
$3.3MNutritional Omics of Pulmonary Function DeclineR01HL149352 · NHLBI · RESEARCH TRIANGLE INSTITUTE · PI CASSANO, PATRICIA A, HANCOCK, DANA B · 2019 to 2022
$3.1MUsing Electrocardiogram Genetics to Inform Arrhythmia RiskR01HL157635 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS, MIRSHAHI, TOORAJ · 2022 to 2025
$2.9MUnderstanding airway mucus dysfunction in population-based studiesR01HL164824 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DIAZ, ALEJANDRO · 2022 to 2025
$2.7MAssessing Alzheimer disease risk and heterogeneity using multimodal machine learning approachesU01AG068221 · NIA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DESTEFANO, ANITA L, LIN, HONGHUANG · 2021 to 2024
$2.5MDeep learning to enable the genetic analysis of aortaK08HL159346 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PIRRUCCELLO, JAMES · 2021 to 2025
$827kAmerican Heart Association-American Stroke Association 18SFRN34110082American Heart Association-American Stroke Association 18SFRN34250007NHLBI NIH HHS K08 HL159346NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL111024NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL139731NHLBI NIH HHS R01 HL149352NHLBI NIH HHS R01 HL157635NHLBI NIH HHS R01 HL164824NIA NIH HHS U01 AG058589NIA NIH HHS U01 AG068221
Abstract
With the emergence of large-scale sequencing data, methods for improving power in rare variant association tests are needed. Here we show that adjusting for common variant polygenic scores improves yield in gene-based rare variant association tests across 65 quantitative traits in the UK Biobank (up to 20% increase at α = 2.6 × 10
Indexed as
Multifactorial InheritanceQuantitative Trait LociGenome-Wide Association StudyModels, GeneticPhenotypePolymorphism, Single Nucleotide
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