Global Alliance for Pharmacogenomics Adds Five New Projects


December 16, 2009

Five new research projects expand an international, collaborative effort to advance understanding of how genetic factors influence a person’s responses to medicines. The additions bring the number of projects in the Global Alliance for Pharmacogenomics to 15.

Launched in April 2008, the alliance combines research expertise from the U.S. NIH Pharmacogenetics Research Network (PGRN, /Research/FeaturedPrograms/PGRN/) with the high-throughput genomic technology and skills of scientists at the Center for Genomic Medicine (CGM, http://www.src.rik​, part of the RIKEN Institute in Japan. All 15 PGRN-RIKEN projects are genome-wide association studies, which simultaneously analyze and compare the sequences of thousands of genes to identify medically relevant differences.

Pharmacogenomics helps doctors pick the right dose of the right medicine for each individual patient.

To benefit other scientists working in this research area, NIH and RIKEN make the data generated by the alliance publicly available through dbGaP (, a database developed by the NIH’s National Center for Biotechnology Information. Study participants have consented to the inclusion of their genetic data, and personal identifying information is not shared.

The long-term goal of pharmacogenomics research is to provide doctors with information that enables them to tailor treatments to each patient. The new studies will contribute by focusing on drugs used to treat major diseases affecting large numbers of people:

Depression is a common psychiatric disease and one of the most prevalent illnesses worldwide. The principal medicines used to treat depression are the selective serotonin reuptake inhibitors (SSRIs), but nearly 50 percent of people fail to respond to them. This project seeks to uncover the genetic basis of SSRI efficacy and side effects by analyzing the DNA of several hundred people who were treated at the Mayo Clinic in Minnesota over the past 4 years.

This project aims to shed light on the puzzling observation that suppressing HIV with antiretroviral medicines fails to revive the immune system in some people. Using DNA samples and data from several hundred patients from the Mbarara Hospital HIV Clinic in Uganda, the study will test the idea that genetic determinants account for variability in immune system recovery among people being treated for HIV.

To control their blood pressure 35-40 million people worldwide take ACE inhibitor drugs. Occasionally, ACE inhibitors trigger a serious reaction characterized by swelling of the mouth, throat, hands or abdominal organs. People who develop the reaction risk suffocation and are often hospitalized. This study aims to identify gene variants and drug combinations that increase a person’s risk of this reaction. The information gained will help doctors avoid this dangerous side effect in high-risk patients.

Atrial Fibrillation
Atrial fibrillation is an abnormal heart rhythm that can cause serious problems such as blood clots and heart failure. This study aims to identify genes that influence how a person responds to medicines used to control the rapid heart rate that characterizes the condition. Understanding the genetic underpinnings of the response will help doctors prescribe the most effective medicine for each patient and may lead to the development of new medicines.

Colorectal Cancer
Recent studies have shown that nonsteroidal anti-inflammatory drugs like Celebrex ®
(celecoxib) help prevent colorectal lesions that can lead to cancer. But in some people, the medicine causes harmful gastrointestinal and cardiovascular side effects. This project aims to uncover genetic factors that affect the efficacy and safety of Celebrex in preventing precancerous colorectal lesions. This knowledge will enable doctors to avoid using Celebrex in people unlikely to benefit from the drug or those at increased risk of side effects.

Title: ACE Inhibitors and Andiogedema
Principal investigators: Drs. N. Brown, D. Roden, S. Williams, C. Ingram, R. Krauss, C. McCarty, with Dr. M. Kubo
Approximate number of samples: 818
Title: Antiretrovirals for HIV Infection in Uganda
Principal investigators: Drs. D. Kroetz, D. Bangsberg, J. Martin, P. Hunt, E. Jorgenson, J. Witte, H. McLeod, M. Wagner, with Dr. T. Mushiroda
Approximate number of samples: 500+
Title: Celecoxib Effectiveness for Colorectal Cancer
Principal investigators: Drs. M. Bertagnolli, S. Weiss, J. Su, M. Ratain, K. Owzar, with Dr. K. Matsuda
Approximate number of samples: 1660
Title: Citalopram and Escitalopram for Depression
Principal investigators: D. Mrazek, C. Schaefer, D. Schaid, K. Giacomini, and R. Weinshilboum, with Dr. T. Mushiroda
Approximate number of samples: 500+
Title: AV Nodal Blocking Agents for Atrial Fibrillation
Principal investigators: Drs. D. Darbar, D. Roden, M. Province, M. Ritchie, H. Okafor, P. Ellinor, S. Kabb, H. Watanabe, with Dr. T. Tanaka
Approximate number of samples: 2000