. 2024 Jan 4;111(1):11-23.

doi: 10.1016/j.ajhg.2023.12.001.

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine

Laura K Wiley¹, Jonathan A Shortt¹, Emily R Roberts², Jan Lowery³, Elizabeth Kudron⁴, Meng Lin¹, David Mayer¹, Melissa Wilson¹, Tonya M Brunetti², Sameer Chavan², Tzu L Phang², Nikita Pozdeyev⁵, Joseph Lesny², Stephen J Wicks², Ethan T Moore², Joshua L Morgenstern², Alanna N Roff², Elise L Shalowitz², Adrian Stewart², Cole Williams², Michelle N Edelmann², Madelyne Hull², J Tacker Patton², Lisen Axell⁶, Lisa Ku⁶, Yee Ming Lee⁷, Jean Jirikowic⁸, Anna Tanaka⁸, Emily Todd⁹, Sarah White⁸, Brett Peterson², Emily Hearst⁸, Richard Zane¹⁰, Casey S Greene¹, Rasika Mathias², Marilyn Coors², Matthew Taylor¹¹, Debashis Ghosh¹², Michael G Kahn², Ian M Brooks¹, Christina L Aquilante¹³, David Kao¹⁴, Nicholas Rafaels², Kristy R Crooks¹⁵, Steve Hess⁸, Kathleen C Barnes¹⁶, Christopher R Gignoux¹⁷

Affiliations

¹ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
² Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
³ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Community and Behavioral Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁴ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁵ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁶ CU Cancer Center, Hereditary Cancer Clinic, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁷ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁸ UCHealth, Aurora, CO 80045, USA.
⁹ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; UCHealth, Aurora, CO 80045, USA.
¹⁰ UCHealth, Aurora, CO 80045, USA; University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹¹ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Cardiology, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹² Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA.
¹³ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹⁴ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Cardiology, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; CARE Innovation Center, UCHealth, Aurora, CO 80045, USA.
¹⁵ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pathology, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹⁶ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: kathleen.barnes@cuanschutz.edu.
¹⁷ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: chris.gignoux@cuanschutz.edu.

PMID: 38181729
PMCID: PMC10806731
DOI: 10.1016/j.ajhg.2023.12.001

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine

Laura K Wiley et al. Am J Hum Genet. 2024.

. 2024 Jan 4;111(1):11-23.

doi: 10.1016/j.ajhg.2023.12.001.

Authors

Affiliations

¹ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
² Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
³ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Community and Behavioral Health, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁴ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁵ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁶ CU Cancer Center, Hereditary Cancer Clinic, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁷ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁸ UCHealth, Aurora, CO 80045, USA.
⁹ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; UCHealth, Aurora, CO 80045, USA.
¹⁰ UCHealth, Aurora, CO 80045, USA; University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹¹ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Cardiology, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹² Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO 80045, USA.
¹³ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹⁴ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Division of Cardiology, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; CARE Innovation Center, UCHealth, Aurora, CO 80045, USA.
¹⁵ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pathology, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
¹⁶ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: kathleen.barnes@cuanschutz.edu.
¹⁷ Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA. Electronic address: chris.gignoux@cuanschutz.edu.

PMID: 38181729
PMCID: PMC10806731
DOI: 10.1016/j.ajhg.2023.12.001

Abstract

Precision medicine initiatives across the globe have led to a revolution of repositories linking large-scale genomic data with electronic health records, enabling genomic analyses across the entire phenome. Many of these initiatives focus solely on research insights, leading to limited direct benefit to patients. We describe the biobank at the Colorado Center for Personalized Medicine (CCPM Biobank) that was jointly developed by the University of Colorado Anschutz Medical Campus and UCHealth to serve as a unique, dual-purpose research and clinical resource accelerating personalized medicine. This living resource currently has more than 200,000 participants with ongoing recruitment. We highlight the clinical, laboratory, regulatory, and HIPAA-compliant informatics infrastructure along with our stakeholder engagement, consent, recontact, and participant engagement strategies. We characterize aspects of genetic and geographic diversity unique to the Rocky Mountain region, the primary catchment area for CCPM Biobank participants. We leverage linked health and demographic information of the CCPM Biobank participant population to demonstrate the utility of the CCPM Biobank to replicate complex trait associations in the first 33,674 genotyped individuals across multiple disease domains. Finally, we describe our current efforts toward return of clinical genetic test results, including high-impact pathogenic variants and pharmacogenetic information, and our broader goals as the CCPM Biobank continues to grow. Bringing clinical and research interests together fosters unique clinical and translational questions that can be addressed from the large EHR-linked CCPM Biobank resource within a HIPAA- and CLIA-certified environment.

Keywords: biobanking; electronic health records; learning health system; pharmacogenomics; precision medicine.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests K.C.B. owns stock in Tempus and Galatea Bio and is an employee of Oxford Nanopore Technologies. C.R.G. owns stock in 23andMe, Inc.

Figures

**Figure 1**
Cumulative enrollment and sample collection of CCPM Biobank participants over time Enrollment shown in blue and sample collection in red.

**Figure 2**
Density of recruitment of CCPM Biobank participants Density across (A) the USA and (B) Colorado shown, at the level of the first three digits of zip codes.

**Figure 3**
CCPM Biobank participant proportional phecode use by domain and specific phecode as derived from the EHR across participants in the entire CCPM Biobank Domain shown at left and phecode at right.

**Figure 4**
Ancestry and population structure estimates in the CCPM Biobank (A) Counts of closely related pairs of individuals as determined by PONDEROSA. (B) Principal components analysis of CCPM Biobank participants (gray points) overlaid with individuals from a global reference panel (colored points). (C) Admixture estimates for CCPM Biobank participants from the five largest EHR race/ethnicity categories. 1000 Genomes and Human Genome Diversity Project (HGDP) data are provided for reference.

**Figure 5**
Replication of known associations in the CCPM Biobank across a range of traits, comparing CCPM Biobank findings with REGENIE to those found in the GWAS catalog. Error bars represent the 95% confidence interval for the odds ratio For all, the risk-increasing allele is compared, and with multiple reporters, the largest dataset in the GWAS catalog was used for reference. OMIM identifiers for nearest genes are as follows: *APOE* (MIM: 107741), *SMAD3* (MIM: 603109), *TERT* (MIM: 187270), *HCG22* (MIM: 613918), *PTCSC2* (MIM: N/A), *HLA-DRA* (MIM: 142860), *FTO* (MIM: 610966), *HCP5* (MIM: 604676), *HLA-DRB1* (MIM: 142857), *HLA-DQB1* (MIM: 604305), and *TCF7L2* (MIM: 602228).

See this image and copyright information in PMC

References

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Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine

Affiliations

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

Full Text Sources