Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing

Thomas R Austin^{1

2}, Caitlin P McHugh³, Jennifer A Brody^{4

5}, Joshua C Bis^{4

5}, Colleen M Sitlani^{4

5}, Traci M Bartz^{4

5

6}, Mary L Biggs^{4

6}, Nisha Bansal⁷, Petra Buzkova⁶, Steven A Carr⁸, Christopher R deFilippi⁹, Mitchell S V Elkind¹⁰, Howard A Fink¹¹, James S Floyd^{4

12

5}, Alison E Fohner^{4

12

13}, Robert E Gerszten¹⁴, Susan R Heckbert^{4

12}, Daniel H Katz¹⁴, Jorge R Kizer^{15

16

17

18}, Rozenn N Lemaitre^{4

5}, W T Longstreth^{12

19}, Barbara McKnight⁵, Hao Mei²⁰, Kenneth J Mukamal²¹, Anne B Newman²², Debby Ngo²¹, Michelle C Odden²³, Ramachandran S Vasan^{24

25}, Ali Shojaie⁶, Noah Simon⁶, George Davey Smith²⁶, Neil M Davies^{26

27

28}, David S Siscovick²⁹, Nona Sotoodehnia^{4

30}, Russell P Tracy³¹, Kerri L Wiggins^{4

5}, Jie Zheng²⁶, Bruce M Psaty^{4

12

5

32}

Affiliations

¹ Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA. austintr@uw.edu.
² Department of Epidemiology, University of Washington, Seattle, WA, USA. austintr@uw.edu.
³ Alzheimer's Disease Data Initiative, Kirkland, WA, USA.
⁴ Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁷ Division of Nephrology, University of Washington, Seattle, WA, USA.
⁸ Broad Institute of MIT and Harvard, Boston, MA, USA.
⁹ Inova Heart and Vascular Institute, Falls Church, VA, USA.
¹⁰ Department of Neurology, Columbia University, New York, NY, USA.
¹¹ Geriatric Research Education & Clinical Center, Minneapolis VA Healthcare System, Minneapolis, MN, USA.
¹² Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹³ Institute of Public Health Genetics, University of Washington, Seattle, WA, USA.
¹⁴ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁵ Cardiology Section, San Francisco VA Health Care System, San Francisco, CA, USA.
¹⁶ Department of Biostatistics, University of California San Francisco, San Francisco, CA, USA.
¹⁷ Department of Epidemology, University of California San Francisco, San Francisco, CA, USA.
¹⁸ Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
¹⁹ Department of Neurology, University of Washington, Seattle, WA, USA.
²⁰ Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
²¹ Beth Israel Deaconess Medical Center, Boston, MA, USA.
²² Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
²³ Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.
²⁴ Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA.
²⁵ Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
²⁶ MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
²⁷ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Norwegian, Norway.
²⁸ Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
²⁹ The New York Academy of Medicine, New York, NY, USA.
³⁰ Division of Cardiology, University of Washington, Seattle, WA, USA.
³¹ Departments of Pathology & Laboratory Medicine, and Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
³² Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.

PMID: 35790642
PMCID: PMC9255954
DOI: 10.1007/s10654-022-00888-z

Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing

Thomas R Austin et al. Eur J Epidemiol. 2022 Jul.

. 2022 Jul;37(7):755-765.

doi: 10.1007/s10654-022-00888-z. Epub 2022 Jul 5.

Authors

Affiliations

¹ Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA. austintr@uw.edu.
² Department of Epidemiology, University of Washington, Seattle, WA, USA. austintr@uw.edu.
³ Alzheimer's Disease Data Initiative, Kirkland, WA, USA.
⁴ Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
⁵ Department of Medicine, University of Washington, Seattle, WA, USA.
⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
⁷ Division of Nephrology, University of Washington, Seattle, WA, USA.
⁸ Broad Institute of MIT and Harvard, Boston, MA, USA.
⁹ Inova Heart and Vascular Institute, Falls Church, VA, USA.
¹⁰ Department of Neurology, Columbia University, New York, NY, USA.
¹¹ Geriatric Research Education & Clinical Center, Minneapolis VA Healthcare System, Minneapolis, MN, USA.
¹² Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹³ Institute of Public Health Genetics, University of Washington, Seattle, WA, USA.
¹⁴ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁵ Cardiology Section, San Francisco VA Health Care System, San Francisco, CA, USA.
¹⁶ Department of Biostatistics, University of California San Francisco, San Francisco, CA, USA.
¹⁷ Department of Epidemology, University of California San Francisco, San Francisco, CA, USA.
¹⁸ Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
¹⁹ Department of Neurology, University of Washington, Seattle, WA, USA.
²⁰ Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
²¹ Beth Israel Deaconess Medical Center, Boston, MA, USA.
²² Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
²³ Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.
²⁴ Department of Epidemiology, School of Public Health, Boston University, Boston, MA, USA.
²⁵ Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
²⁶ MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
²⁷ K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Norwegian, Norway.
²⁸ Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
²⁹ The New York Academy of Medicine, New York, NY, USA.
³⁰ Division of Cardiology, University of Washington, Seattle, WA, USA.
³¹ Departments of Pathology & Laboratory Medicine, and Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
³² Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.

PMID: 35790642
PMCID: PMC9255954
DOI: 10.1007/s10654-022-00888-z

Abstract

Background: In the last decade, genomic studies have identified and replicated thousands of genetic associations with measures of health and disease and contributed to the understanding of the etiology of a variety of health conditions. Proteins are key biomarkers in clinical medicine and often drug-therapy targets. Like genomics, proteomics can advance our understanding of biology.

Methods and results: In the setting of the Cardiovascular Health Study (CHS), a cohort study of older adults, an aptamer-based method that has high sensitivity for low-abundance proteins was used to assay 4979 proteins in frozen, stored plasma from 3188 participants (61% women, mean age 74 years). CHS provides active support, including central analysis, for seven phenotype-specific working groups (WGs). Each CHS WG is led by one or two senior investigators and includes 10 to 20 early or mid-career scientists. In this setting of mentored access, the proteomic data and analytic methods are widely shared with the WGs and investigators so that they may evaluate associations between baseline levels of circulating proteins and the incidence of a variety of health outcomes in prospective cohort analyses. We describe the design of CHS, the CHS Proteomics Study, characteristics of participants, quality control measures, and structural characteristics of the data provided to CHS WGs. We additionally highlight plans for validation and replication of novel proteomic associations.

Conclusion: The CHS Proteomics Study offers an opportunity for collaborative data sharing to improve our understanding of the etiology of a variety of health conditions in older adults.

Keywords: Cardiovascular Disease; Cohort Study; Genomics; Proteomics.

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Conflict of interest statement

Psaty serves on the Steering Committee for the Yale Open Data Access Project funded by Johnson & Johnson. Elkind receives study drug in kind from the BMS-Pfizer Alliance for Eliquis® and funding from Roche for a NIH-funded stroke prevention trial; royalties from UpToDate for chapters on stroke; and serves as an unpaid Officer of the American Heart Association. Floyd has consulted for Shionogi Inc. Kizer has stock ownership in Abbott, Bristol Myers Squibb, Johnson & Johnson, Medtronic, Merck and Pfizer. Odden is a consultant for Cricket Health, Inc.

Figures

**Fig. 1**
Flowchart of Inclusion in Cardiovascular Health Study proteomics analyses CHS = Cardiovascular Health Study QC = Quality Control

**Fig. 2**
Comparison of log-transformed and standardized SomaLogic aptamer levels and CHS-assayed biomarkers for (A) C-reactive protein (n = 3,158), (B) Cystatin C (n = 3,182), (C) Factor VII (n = 3,129), (D) Fibrinogen (n = 3,175), and (E) NT-proBNP (n = 2,837)

**Fig. 3**
Boxplots of median relative fluorescence unit for each participant sample, stratified by plate.RFU = relative fluorescence unit

See this image and copyright information in PMC

References

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Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing

Affiliations

Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing

Authors

Affiliations

Abstract

Conflict of interest statement

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