The eMERGE PGx Project

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The eMERGE PGx project:   A multi-center pilot of pharmacogenetic sequencing in clinical practice

eMERGE-PGx is a multi-site test of the concept that sequence information can be coupled to electronic medical records (EMRs) for use in healthcare. The promise of personalized medicine - health care guided by each individual’s biological characteristics - is being fostered by increasingly powerful and economical methods to acquire clinically relevant biomarkers from large numbers of people. One therapeutic area that seems especially ripe for an early test of the personalized medicine concept is pharmacogenomics (PGx) – the idea that individual variation in drug response includes a genomic component. Drug response variation is an accepted feature of virtually all drug treatments, and contemporary molecular biologic tools continue to identify key genes mediating drug metabolism, transport, and targets. Importantly, common variation in these genes is an increasingly well-recognized contributor, sometimes with large effects, to variation in drug responses. As a result, recommendations for genotype-guided therapy are increasing. These evidence-based recommendations, if implemented in health care practice, could reduce adverse drug events and improve time to therapeutic response. Through eMERGE-PGx, we are developing strategies for the optimal implementation of genetic sequence data into the clinical environment with the ultimate goal of improving patient care.

Sequencing and phenotype data (demographics, medications, and ICD-9 and CPT codes) are being gathered into a variant repository. SPHINX, the Sequence, Phenotype, and Pharmacogenomics Integration Exchange (SPHINX) is a web-based tool for exploring these data for hypothesis generation, especially around drug response implications of genetic variation across the eMERGE PGx project cohort. Access SPHINX using the SPHINX tab at the top of this page.

Project Plan:

 

 


Site Implementation Comparisons:

The 9 sites are implementing the project plan with institution-specific variation. Some similarities and differences are highlighted below. Clicking on the pictures accesses comparative details related to that specific area of the project.


Sequencing Information:

At the heart of the eMERGE PGx project is the sequencing platform, PGRNSeq, developed by the PGRN Network. PGRNSeq was developed in a cooperation between Deep Sequencing Resources at the Baylor College of Medicine and the University of Washington to fully characterize the genetic variation across human populations in 84 Very Important Pharmacogenes (the VIP list of genes). 


Implementation of well-established pharmacogenetic genotypes into the EHR, by eMERGE-PGx Site:

Site CPIC Gene/Drug Pairs
Boston Children's Hospital (BCH)

TPMT / Thiopurines

CYP2C9 / warfarin

VKORC1 / warfarin

CYP2C9 / Phenytoin/Fosphenytoin

Children's Hospital of Philidelphia (CHOP)

CYP2D6 / codeine

TPMT / thiopurines

HLAB1502 / carbamazepine

Additional CPIC and Duth Pharmacogenetics Working Group Recommendations

Cincinnati Children's Hospital Medical Center (CCHMC)

CYP2D6 / codeine

CYP2C9 / warfarin

VKORC1 / warfarin

CYP2D6 / tricyclic antidepressants

CYP2D6 / SSRIs

TPMT / thiopurines

Geisinger Health System (GHS)

CYP2C19 / clopidogrel

CYP2C9 / warfarin

VKORC1 / warfarin

SLCO1B1 / simvastatin

IL28B / interferon response

Group Health/ University of Washington HLAB1502 / carbamazepine
Marshfield Clinic

CYP2C19 / clopidogrel

CYP2C9 / warfarin

VKORC1 / warfarin

SLCO21B1 / simvastatin

Mayo Clinic

CYP2C19 / clopidogrel

CYP2C9 / warfarin

VKORC1 / warfarin

SLCO21B1 / simvastatin

CYP2D6 / codeine

CYP2D6 / tramadol

CYP2D6 / tamoxifen

Icahn School of Medicine at Mt. Sinai

CYP2C19 / clopidogrel

CYP2C9 / warfarin

VKORC1 / warfarin

SLCO21B1 / simvastatin

Northwestern University

CYP2C19 / clopidogrel

CYP2C9 / warfarin

VKORC1 / warfarin

SLCO21B1 / simvastatin

Vanderbilt University

CYP2C19 / clopidogrel

CYP2C9 / warfarin

VKORC1 / warfarin

TPMT / thiopurines