ArticleAmerican journal of human genetics2022
Integration of rare expression outlier-associated variants improves polygenic risk prediction.
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Article in American journal of human genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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22 citing papers in PubMed, 29 citations in OpenAlex.
- GeneSIS: enhancing transferability of polygenic scores with variant-level gene-by-sex interaction effects.bioRxiv : the preprint server for biology · 2026Article
- Decoding common and rare noncoding variant effects across cellular and developmental contexts.Nature genetics · 2026Article
- Paired DNA and RNA sequencing uncovers common and rare variation regulating human retinal gene expression.Nature communications · 2026Article
- Deep learning-based stratification of Schizophrenia Spectrum Disorder from real-world data reveals distinct profiles of common and rare variant genetic signal.medRxiv : the preprint server for health sciences · 2026Article
- Clinical use of polygenic risk scores: current status, barriers and future directions.Nature reviews. Genetics · 2026Review
- From polygenic risk to digital twins: the future of personalised cardiovascular medicine.Frontiers in cardiovascular medicine · 2026Review
- Studying rare variant polygenic risk scores using whole exome sequencing and imputed genotype data.Communications biology · 2025Article
- Transcriptome-wide outlier approach identifies individuals with minor spliceopathies.American journal of human genetics · 2025Article
- Aberrant gene expression prediction across human tissues.Nature communications · 2025Article
- Mapping the regulatory effects of common and rare non-coding variants across cellular and developmental contexts in the brain and heart.bioRxiv : the preprint server for biology · 2025Article
- Review
- GREGoR: Accelerating Genomics for Rare Diseases.ArXiv · 2024Article
- Polygenic prediction for underrepresented populations through transfer learning by utilizing genetic similarity shared with European populations.Briefings in bioinformatics · 2024Article
- Misexpression of inactive genes in whole blood is associated with nearby rare structural variants.American journal of human genetics · 2024Article
- A polygenic score method boosted by non-additive models.Nature communications · 2024Article
- Genetic modifiers of rare variants in monogenic developmental disorder loci.Nature genetics · 2024Article
- Evaluation of Genetic or Cellular Impairments in Type I IFN Immunity in a Cohort of Young Adults with Critical COVID-19.Journal of clinical immunology · 2024Article
- CADD v1.7: using protein language models, regulatory CNNs and other nucleotide-level scores to improve genome-wide variant predictions.Nucleic acids research · 2024Article
- Whole exome sequencing identifies a novel mutation inFrontiers in medicine · 2024Article
- The functional impact of rare variation across the regulatory cascade.Cell genomics · 2023Article
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 2 countries.
Craig SmailDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA; Genomic Medicine Center, Children's Mercy Research Institute and Children's Mercy Kansas City, Kansas City, MO, USA. Electronic address: csmail@cmh.edu.
Nicole M FerraroDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Qin HuiAtlanta VA Health Care System, Decatur, GA, USA; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Matthew G DurrantDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Matthew AguirreDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Yosuke TanigawaDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Marissa R Keever-KeigherGenomic Medicine Center, Children's Mercy Research Institute and Children's Mercy Kansas City, Kansas City, MO, USA.
Abhiram S RaoDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA.
Johanne M JustesenDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Xin LiCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
Michael J GloudemansDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Themistocles L AssimesPalo Alto VA Health Care System, Palo Alto, CA, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Charles KooperbergPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, WA, USA.
Jie HuangSchool of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Christopher J O'DonnellBoston VA Health Care System, Boston, MA, USA; Division of Cardiology, Department of Medicine, Harvard Medical School, Boston, MA, USA; Division of Cardiology, Department of Medicine, Brigham Women's Hospital, Boston, MA, USA.
Yan V SunAtlanta VA Health Care System, Decatur, GA, USA; Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA, USA.
Million Veteran Program
Manuel A RivasDepartment of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA.
Stephen B MontgomeryDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: smontgom@stanford.edu.
Stanford University · USEmory University · USMercy Research · USBrigham and Women's Hospital · USChinese Academy of Sciences · CNFred Hutch Cancer Center · USSouthern University of Science and Technology · CNStanford Medicine · USUniversity of Washington · USVA Palo Alto Health Care System · US
Funding
POSTDOCTORAL TRAINING IN MEDICAL INFORMATION SCIENCEST15LM007033 · NLM · STANFORD UNIVERSITY · PI SYLVIA KATINA PLEVRITIS · 1985 to 2026
$25.5MMulti-omic functional assessment of novel AD variants using high-throughput and single-cell technologiesU01AG072573 · NIA · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL, MONTGOMERY, STEPHEN · 2021 to 2025
$8.3MOptimizing imputation for diverse populations in a distributed frameworkU01HG009080 · NHGRI · STANFORD UNIVERSITY · PI KENNY, EIMEAR ELIZABETH · 2016 to 2020
$5.2MMapping Molecular and Phenotypic Interactions in Alzheimers DiseaseR01AG066490 · NIA · STANFORD UNIVERSITY · PI MONTGOMERY, STEPHEN · 2020 to 2024
$3.6MDecoding the regulatory architecture of the human genome across cell types, individuals and diseaseU01HG009431 · NHGRI · STANFORD UNIVERSITY · PI PRITCHARD, JONATHAN K · 2017 to 2021
$3.5MNew methods for constructing and evaluating polygenic scoresR01HG011432 · NHGRI · STANFORD UNIVERSITY · PI PRITCHARD, JONATHAN K · 2020 to 2023
$3.3MIdentifying causal genetic variants and molecular mechanisms impacting mental healthR01MH125244 · NIMH · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL, MONTGOMERY, STEPHEN · 2021 to 2025
$3.0MSOFTWARE FOR LARGE-SCALE INFERENCE OF THE GENETICS OF LIFESTYLE MEASURES, BIOMARKERS, AND COMMON AND RARE DISEASESR01HG010140 · NHGRI · STANFORD UNIVERSITY · PI KUNDAJE, ANSHUL, MONTGOMERY, STEPHEN · 2018 to 2022
$2.0MBiomedical Data Science Graduate Training at StanfordT32LM012409 · NLM · STANFORD UNIVERSITY · PI PLEVRITIS, SYLVIA KATINA · 2016 to 2020
$1.5MPredicting causal non-coding variants in a founder populationR01HG008150 · NHGRI · STANFORD UNIVERSITY · PI MONTGOMERY, STEPHEN · 2015 to 2017
$1.4MIntegrative multi-omics in whole genome studies of HLBS disordersR01HL142015 · NHLBI · STANFORD UNIVERSITY · PI MONTGOMERY, STEPHEN · 2018 to 2019
$882kComputational appliance: a supercomputer for modern biomedical researchS10OD023452 · OD · STANFORD UNIVERSITY · PI DATTA, SOMALEE · 2017 to 2017
$600kBLRD VA I01 BX003340BLRD VA I01 BX003362BLRD VA I01 BX004821Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NHGRI NIH HHS R01 HG008150NHGRI NIH HHS R01 HG010140NHGRI NIH HHS R01 HG011432NHGRI NIH HHS U01 HG009080NHGRI NIH HHS U01 HG009431NHLBI NIH HHS R01 HL142015NIA NIH HHS R01 AG066490NIA NIH HHS U01 AG072573NIH HHS S10 OD023452NIMH NIH HHS R01 MH125244NLM NIH HHS T15 LM007033NLM NIH HHS T32 LM012409
Abstract
Polygenic risk scores (PRSs) quantify the contribution of multiple genetic loci to an individual's likelihood of a complex trait or disease. However, existing PRSs estimate this likelihood with common genetic variants, excluding the impact of rare variants. Here, we report on a method to identify rare variants associated with outlier gene expression and integrate their impact into PRS predictions for body mass index (BMI), obesity, and bariatric surgery. Between the top and bottom 10%, we observed a 20.8% increase in risk for obesity (p = 3 × 10
Indexed as
Multifactorial InheritanceObesityBody Mass IndexGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPhenotypeRisk FactorsBMIcomplex diseaseobesitypolygenic risk scoresrare variantstranscriptomics
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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.