NHLBI Trans-Omics for Precision Medicine
Overview
The NHLBI Trans-Omics for Precision Medicine (TOPMed) program is a major initiative by the National Heart, Lung, and Blood Institute to generate scientific resources that enhance understanding of fundamental biological processes underlying heart, lung, blood, and sleep (HLBS) disorders. TOPMed combines whole genome sequencing with extensive phenotypic characterization across diverse populations, creating one of the largest and most comprehensive genomic medicine resources.
Program Scope
Data Generation
- Whole Genome Sequencing: Deep coverage WGS from diverse cohorts
- Multi-Omics: RNA-seq, metabolomics, proteomics, epigenomics
- Sample Size: Over 180,000 individuals sequenced
- Diversity: Represents multiple ancestries and ethnic backgrounds
- Phenotyping: Extensive clinical and phenotypic data
Focus Areas
- Cardiovascular diseases
- Pulmonary disorders
- Hematologic conditions
- Sleep disorders
- Risk factor assessment (blood pressure, lipids, etc.)
Key Features
- Population Diversity: Includes underrepresented populations in genomic research
- Longitudinal Data: Many cohorts have decades of follow-up
- Deep Phenotyping: Rich clinical, environmental, and lifestyle data
- Reference Panels: High-quality haplotype reference for imputation
- Variant Catalog: Comprehensive catalog of genetic variation
- Integrated Analysis: Links genomic data with multi-omic and phenotypic information
Data Types
Genomic Data
- Whole genome sequences (30-40x coverage)
- Variant calls (SNVs, indels, structural variants)
- Haplotype phasing
- Reference panels for genotype imputation
Phenotypic Data
- Disease diagnoses and outcomes
- Quantitative traits (blood pressure, lipids, lung function, etc.)
- Electronic health records
- Medication history
- Environmental exposures
- Lifestyle factors
Multi-Omic Data
- RNA sequencing (gene expression)
- Metabolomics profiles
- Proteomic measurements
- Epigenetic marks (DNA methylation)
Applications
Precision Medicine
- Genetic risk prediction for HLBS diseases
- Pharmacogenomics and treatment response
- Disease subtype classification
- Personalized intervention strategies
Scientific Discovery
- Novel gene-disease associations
- Rare variant identification
- Pleiotropy and genetic correlation analysis
- Functional genomics insights
- Population genetics and evolution
Clinical Translation
- Biomarker discovery
- Drug target identification
- Clinical trial design
- Diagnostic test development
Data Access
dbGaP Repository
- Controlled-access individual-level data
- Phenotype and genotype files
- Application process for researchers
Public Resources
- Summary statistics
- Allele frequencies (TOPMed Bravo variant browser)
- Reference panels for imputation
- Analysis pipelines and tools
Participating Cohorts
TOPMed includes data from numerous established cohort studies:
- Framingham Heart Study
- Jackson Heart Study
- Multi-Ethnic Study of Atherosclerosis (MESA)
- Women’s Health Initiative (WHI)
- Genetic Studies of Atherosclerosis Risk (GeneSTAR)
- And many others
Computational Resources
- Analysis Pipelines: Standardized workflows for variant calling, QC, and analysis
- Cloud Computing: Integration with cloud platforms (BioData Catalyst)
- Tools and Software: Open-source analysis tools
- Imputation Server: TOPMed Imputation Server for genotype imputation
This resource has the Information Resource identifier: infores:topmed
Access
- Homepage: https://topmed.nhlbi.nih.gov/
- Data Access: https://www.ncbi.nlm.nih.gov/gap/ (dbGaP)
- Variant Browser: https://bravo.sph.umich.edu/freeze8/hg38/
- Imputation Server: https://imputation.biodatacatalyst.nhlbi.nih.gov/
For more information about TOPMed and data access, visit https://topmed.nhlbi.nih.gov/