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NIH Expands Network Focused on How Genes Affect Drug Responses

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The National Institutes of Health plans to spend $161.3 million over the next five years to expand the Pharmacogenomics Research Network (PGRN), a nationwide collaborative of scientists focused on understanding how genes affect a person's response to medicines.

"Thanks to breakthroughs in genome sequencing technologies and our growing understanding of genetic variation among individuals, there has never been a better time to propel the field of pharmacogenomics," said NIH Director Francis S. Collins, M.D., Ph.D. "Through these studies, we are moving closer to the goal of using genetic information to help prescribe the safest, most effective medicine for each patient."

Spearheaded by the NIH's National Institute of General Medical Sciences (NIGMS) and launched in 2000, the PGRN has already identified gene variants linked to responses to medicines for different cancers, heart disease, asthma, nicotine addiction and other conditions.

The expanded network will continue research in these areas and move into new ones, including rheumatoid arthritis and bipolar disorder. Network scientists will also develop novel research methods and study the use of pharmacogenetics in rural and underserved populations.

The new awards include 14 scientific research projects and seven network resources. The resources will benefit PGRN scientists by:

- offering deep DNA sequencing capacity by partnering with experts in this field
- providing statistical analysis expertise
- developing standardized terminology for pharmacogenomics research
- piloting ways to learn about pharmacogenomics from de-identified medical records in health care systems
- continuing and expanding a 2-year-old international collaboration with the Center for Genomic Medicine at the RIKEN Institute in Yokohama, Japan.

RESEARCH GROUPS:

The PGRN research group projects are listed below alphabetically by principal investigator. Also included are the anticipated five-year total costs for each grant.

Kathleen M. Giacomini, University of California, San Francisco, $11.9 million, Pharmacogenomics of Membrane Transporters (the Global Alliance for Pharmacogenomics resource listed below is also associated with this award)

Julie A. Johnson, University of Florida, Gainesville, $9.8 million, Pharmacogenomic Evaluation of Antihypertensive Responses

John R. Kelsoe, University of California, San Diego, $6.4 million, Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder

Ronald M. Krauss, Children's Hospital Oakland Research Institute (Calif.), $9.4 million, Pharmacogenomics and Risk of Cardiovascular Disease (the Human Exome Resequencing resource listed below is also associated with this award)

Caryn Lerman, University of Pennsylvania, Philadelphia, and Rachel F. Tyndale, University of Toronto,   $12 million, Pharmacogenetics of Nicotine Addiction Treatment

Robert M. Plenge, Brigham and Women's Hospital, Boston, $7.5 million, Genetic Predictors of Response to Anti-TNF Therapy in Rheumatoid Arthritis

Mark J. Ratain, Nancy J. Cox and M. Eileen Dolan, University of Chicago, $10.3 million, PAAR--Pharmacogenomics of Anticancer Agents Research Group

Mary V. Relling, St. Jude Children's Research Hospital, Memphis, Tenn., $8.6 million, PAAR4Kids--Pharmacogenomics of Anticancer Agents Research in Children

Dan M. Roden, Vanderbilt University School of Medicine, Nashville, Tenn., $12.4 million, Pharmacogenomics of Arrhythmia Therapy (two resources listed below-PGRN Statistical Analysis Resource and Pharmacogenomic Discovery and Replication in Very Large Populations-are also associated with this award)

Wolfgang Sadee, Ohio State University, Columbus, $9.1 million, Expression Genetics in Drug Therapy

Alan R. Shuldiner, University of Maryland, Baltimore, $11.4 million, Pharmacogenomics of Anti-Platelet Intervention-2 (PAPI-2) Study

Kenneth E. Thummel and Wylie G. Burke, University of Washington, Seattle, $10.2 million, Pharmacogenetics in Rural and Underserved Populations

Richard M. Weinshilboum, Mayo Clinic, Rochester, Minn., $11.2 million, Pharmacogenetics of Phase II Drug Metabolizing Enzymes (two resources listed below-Next Generation DNA Sequencing and Pharmacogenomic Ontology Network Resource-are also associated with this award)

Scott T. Weiss and Kelan G. Tantisira, Brigham and Women's Hospital, Boston, $9.8 million, Pharmacogenetics of Asthma Treatment

NETWORK RESOURCES:

The PGRN resources are listed below along with their anticipated five-year grant total costs. The scientists leading each effort are listed alphabetically.

Global Alliance for Pharmacogenomics, $3.2 million
Kathleen M. Giacomini, University of California, San Francisco

Next Generation DNA Sequencing, $2.3 million
Richard Gibbs, Baylor College of Medicine, Houston

Next Generation Sequencing, $3.0 million
Elaine Mardis, Washington University, St. Louis

Human Exome Resequencing, $3.9 million
Deborah A. Nickerson, University of Washington School of Medicine, Seattle

PGRN Statistical Analysis Resource, $2.4 million
Marylyn Ritchie, Vanderbilt University, Nashville

Pharmacogenomic Discovery and Replication in Very Large Populations, $3.4 million
Dan M. Roden, Vanderbilt University Medical Center, Nashville

Pharmacogenomic Ontology Network Resource, $3.1 million
Christopher Chute, Mayo Clinic, Rochester

The PGRN is funded by nine NIH components: NIGMS; the National Heart, Lung, and Blood Institute; the National Cancer Institute; the National Institute on Drug Abuse; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; the National Human Genome Research Institute; the National Institute of Mental Health; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and the Office of Research on Women's Health in the Office of the Director.