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A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience

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Abstract

The CATHeterization GENetics (CATHGEN) biorepository was assembled in four phases. First, project start-up began in 2000. Second, between 2001 and 2010, we collected clinical data and biological samples from 9334 individuals undergoing cardiac catheterization. Samples were matched at the individual level to clinical data collected at the time of catheterization and stored in the Duke Databank for Cardiovascular Diseases (DDCD). Clinical data included the following: subject demographics (birth date, race, gender, etc.); cardiometabolic history including symptoms; coronary anatomy and cardiac function at catheterization; and fasting chemistry data. Third, as part of the DDCD regular follow-up protocol, yearly evaluations included interim information: vital status (verified via National Death Index search and supplemented by Social Security Death Index search), myocardial infarction (MI), stroke, rehospitalization, coronary revascularization procedures, medication use, and lifestyle habits including smoking. Fourth, samples were used to generate molecular data. CATHGEN offers the opportunity to discover biomarkers and explore mechanisms of cardiovascular disease.

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Abbreviations

CATHGEN:

CATHeterization GENetics; sample and clinical data repository

dbGaP:

NCBI’s database of genotypes and phenotypes

DDCD:

Duke Databank for Cardiovascular Diseases; clinical database

DISCERN:

Duke search engine for clinical data from patient records

DNA:

Deoxyribonucleic acid

EDTA:

Ethylenediaminetetraacetic acid; anticoagulant

GWAS:

Genome-wide association study

IRB:

Institutional Review Board

LD:

Linkage disequilibrium

LDL-C:

Low-density lipoprotein-cholesterol

MAF:

Minor allele frequency

MS:

Mass spectrometry

MURDOCK Study:

Contiguous sample of 2024 CATHGEN participants

NCBI:

National Center for Biotechnology Information

NEFA:

Non-esterified fatty acids

PEDIGENE®:

Data repository for clinical and sample data

QTL:

Quantitative trait locus

RNA:

Ribonucleic acid

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Acknowledgments

Collections and generation of molecular data were generated in part through research agreements with the following: BG Medicine, Inc.; CardioDx, Inc.; Qiagen, Inc.; and Liposcience, Inc. GWAs and whole genome gene expression data were generated through NIH-funded studies to WEK (HL101621) and SHS (HL095987). Metabolomic data were generated through grants to SHS (HL095987, AHA Fellow-to-Faculty). An internal grant award from the MURDOCK Study (David H. Murdock Institute for Business and Culture, 1UL1 RR024128 from the National Center for Research Resources NCRR) to LKN was also helpful and appreciated. We wish to thank Dr. Marie Lynn Miranda and the Duke School of the Environment for developing geocoding addresses for CATHGEN participants.

Compliance with Ethical Standards

ᅟ

Funding

Through Duke, collections and generation of molecular data were generated in part through research agreements with the following: BG Medicine, Inc.; CardioDx, Inc.; Qiagen, Inc.; Liposcience, Inc..; and US Environmental Protection Agency. GWAs and whole genome gene expression data were generated through NIH-funded studies to WEK (HL101621) and SHS (HL095987). Metabolomic data were generated through grants to SHS (HL095987, AHA Fellow-to-Faculty).

Conflict of Interest

GSG has a financial interest in CardioDx, Inc. No other authors have potential conflicts of interest.

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

All CATHGEN subjects were consented for participation in the biorepository and cardiovascular related research. Subject consent, data collection, sample collection, and analyses were approved through the Duke Institutional Review Board.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, School of Medicine, Duke University, Durham, NC, 27710, USA

    William E. Kraus, Christopher B. Granger, Michael H. Sketch Jr., Mark P. Donahue, Elizabeth R. Hauser, L. Kristin Newby & Svati H. Shah

  2. Duke Molecular Physiology Institute, School of Medicine, Duke University, 300 N. Duke Street, Durham, NC, 27710, USA

    William E. Kraus, Elizabeth R. Hauser, Carol Haynes, Melissa Hurdle, Z. Elaine Dowdy & Svati H. Shah

  3. Duke Clinical Research Institute, School of Medicine, Duke University, Durham, NC, 27710, USA

    Christopher B. Granger & L. Kristin Newby

  4. Duke Center for Applied Genomics and Precision Medicine, Duke University, Durham, NC, 27710, USA

    Geoffrey S. Ginsburg

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  1. William E. Kraus
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  2. Christopher B. Granger
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  3. Michael H. Sketch Jr.
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Correspondence to William E. Kraus.

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Editor-in-Chief Jennifer L. Hall oversaw the review of this article

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Kraus, W.E., Granger, C.B., Sketch, M.H. et al. A Guide for a Cardiovascular Genomics Biorepository: the CATHGEN Experience. J. of Cardiovasc. Trans. Res. 8, 449–457 (2015). https://doi.org/10.1007/s12265-015-9648-y

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