1. Proteomics: Olink
   • ~5400 proteins via multiplex immunoassays
2. Metabolomics: Metabolon
   • 9000 metabolites (~1000 targeted)
3. Methylomics (DNA methylation): Illumina
   • 935,000 methylated DNA sites

Population: CHS Participants with TOPMed WGS (n=4848)

• With permission for genetic studies of primary aims (CVD and aging)
• Without restriction for use by non-CHS investigators

CHS participants have 1-4 measures across years.

Number of measures by CHS year

* measures designated as Y5 may have come from samples collected Y5, Y6, or Y7; those designated as Y9 may have come from Y9 or Y10

Data Access Mechanisms

1. TOPMed Investigators with access to the TOPMed Exchange area: TOPMed Paper Proposal

• Submit paper proposal via TOPMed (Publications Policy)
  • Multi-Study:
    • Present to TOPMed WG(s)
    • Request Permission from PIs
  • CHS-Only:
    • Single PI-Study Proposal: No WG approval required
• Approval is via PI: Bruce Psaty
  • Either approve directly from e-mail, or,
  • Ask to present at CHS Omics call prior to approval (e.g., if the author has questions about the CHS data or needs advice on relevant phenotypes).
• Data access is via the TOPMed Exchange Area
  • SomaLogic and Olink Proteomics data are currently available
  • Metabolomics and Methylation
• Penultimate draft to CHS via TOPMed Omnibus

2. CHS Investigators without access to the TOPMed Exchange Area: CHS datasets from CHSCC

●      Submit Paper proposal via CHS

●      Approval is via CHS P&P and SC

○      Potentially request to present at Omics call

●      Data access via CHSCC

○      CHS-only dataset from CHSCC with CHS IDNOs

○      Data Transfer Agreement via CHS and recipient institution

●      Penultimate draft to CHS via original paper proposal

3. Other investigators unable to work through TOPMed or CHS:

• Data will be available via dbGaP/BioLINCC
• Investigators can use existing mechanisms to request data
• CHS CC is not involved; paper is not tracked or reviewed by CHS

Acknowledgements

In addition to CHS standard acknowledgements, those obtaining CHS-only data via mechanism 2 should cite TOPMed as the generator of the omics data using this text per TOPMed Acknowledgement Guidelines:

Molecular data for the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung and Blood Institute (NHLBI). <Insert molecular data type (Genome Sequencing, RNASeq, Metabolomics, Methylomics, Proteomics)> for "NHLBI TOPMed: Cardiovascular Health Study (phs001368.v4.p2 was performed at <insert omics/sequencing center name (grant/contract number) from the Table below>. [Repeat this sentence for each TOPMed Study-molecular data type combination as appropriate.]

Core support including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Core support including phenotype harmonization, data management, sample-identity QC, and general program coordination were provided by the TOPMed Data Coordinating Center (R01HL-120393; U01HL-120393; contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed.