About Us

10 years of Public Health Genomics at CDC
1997-2007

2.0 Projects of the National Public Health Genomics

Human Genome Epidemiology Network (HuGENet™)

The Human Genome Project has stimulated a rapid increase in genetic research, leading to many new gene discoveries. To realize the potential of genetic research for disease prevention and health promotion, population-based epidemiologic studies are needed to examine the role of genetic variation in population risk of common diseases and to identify the interactions of genetic variants with modifiable risk factors, such as diet and environmental exposures. The results of these population-based studies will help medical and public health professionals to improve and guide medical, behavioral, and environmental interventions. Epidemiologic studies are also needed to assess the clinical validity of genetic tests, including their predictive value in different populations. Epidemiologic surveillance is also important for monitoring the utilization, safety, and effectiveness of genetic tests in clinical and public health practice.

Human Genome Epidemiology (HuGE)

Human Genome Epidemiology (HuGE) uses population-based epidemiologic methods to examine the relationship of genetic variation with health and disease. HuGE combines approaches from genetic epidemiology, molecular epidemiology, and health services research to estimate key measures and compare them among different populations. These measures include:

• prevalence of gene variants,
  
• relative and absolute risks of disease associated with gene variants,
  
• contribution of gene variants to occurrence of disease (attributable risk),
  
• risk of disease associated with gene-gene and gene-environment interactions,
  
• clinical validity of genetic tests, especially their positive and negative predictive values,
  
• utilization of genetic tests, and
  
• impact of genetic tests and services on morbidity, disability, mortality and health care costs.
  

Building the Knowledge Base

During the last decade, the scientific literature has swelled with genetic association studies of varying size, design, and quality. Increasingly, population-based epidemiologic studies also include genetic analyses. Synthesis and interpretation of human genome epidemiologic information requires coordinated, global collaboration among epidemiologists, clinical geneticists, and basic scientists. Dissemination of research findings depends on broad cooperation and communication among medical and public health professionals from government, academia, industry and consumer organizations worldwide.

Human Genome Epidemiology Network (HuGENet™)

In 1998, OPHG established the Human Genome Epidemiology Network (HuGENet). The goal of HuGENet is to help translate genetic research findings into opportunities for preventive medicine and public health by advancing the synthesis, interpretation, and dissemination of population-based data on human genetic variation in health and disease.
HuGENet has continued to grow as an open collaboration of individuals and organizations from around the world. During the last 5 years, OPHG has been joined by additional HuGENet coordinating centers in Cambridge (United Kingdom), Ottawa (Canada), and Ioannina (Greece). In 2005, HuGENet launched the “Network of Networks,” an informal collaboration among existing research networks and consortia dedicated to the study of genetic factors in common diseases, such as cancer, heart disease, and osteoporosis.

Key Activities

OPHG provides the overall leadership and coordination of HuGENet key activities which include:

HuGENet Web site: Established in 2000, the HuGENet free online resources include a curated, weekly summary of newly published scientific articles on human genome epidemiology, a searchable database (HuGE Pub Lit), case studies for training, and information on HuGE workshops and publications.
(www.cdc.gov/genomics/hugenet)

HuGE reviews: These peer-reviewed, systematic reviews of gene-disease associations are published in partnership with ten scientific journals. HuGE reviews typically point to gaps in existing epidemiologic and clinical knowledge, thus stimulating further research in these areas.

HuGE Published Literature database: Systematic collection of relevant articles cited in PubMed began in October 2000. The database, which is updated weekly, is accessible on the Internet. Users can search the database by gene, health outcome, or environmental factor. Key information about each study is presented, along with a direct link to PubMed’s abstract of the article.

HuGE meetings and workshops: OPHG and other HuGENetTM coordinating centers collaborate to sponsor meetings and workshops that focus on methods development, network building, and training.

HuGE informatics: Research and development focuses on building tools for retrieving, indexing, and classifying published literature cited in PubMed, producing research summaries, and promoting research collaboration. Other tools include an aid for identifying candidate genes and a calculator for estimating parameters for genetic tests.

Training in human genome epidemiology: OPHG has supported student internships, post-graduate fellowships, and career development sabbaticals for training.

Key Accomplishments

HuGE Published Literature database: As of July 1, 2007, this searchable, online database indexes 28,254 research studies, referencing 2,924 genes and 3,507 health outcomes/diseases. It includes 60 HuGE Reviews and 508 meta-analyses. Since its inception in October 2000, the database has had the same full-time curator performing weekly updates.

HuGE Navigator: In July 2007, OPHG launched the beta version of the HuGE Navigator (www.hugenavigator.net), a suite of online applications that mine PubMed to populate the HuGE Published Literature database, identify candidate genes, search for investigators with a particular research focus, and produce knowledge summaries.

HuGENet meetings and workshops: Since 2001, ten international meetings and workshops have focused on methods for evaluating, synthesizing and interpreting population-based data on genetic variation, gene-disease association, and gene-gene and gene-environment interactions. Each of these meetings has produced one or more peer-reviewed publications.
Human Genome Epidemiology: This book, published in 2004 includes chapters by an interdisciplinary, international group of authors. A second edition is underway, with publication planned for 2009.

[A text description of this graphic is also available.]

HuGENet Network of Networks: The meeting in 2005 convened members of approximately 30 research networks, ranging from funded consortia to informal collaborating groups. Selected networks are currently piloting approaches to pooled data analysis and knowledge synthesis.

HuGENet Roadmap: Published in Nature Genetics in January 2006, the roadmap outlines an approach to building the knowledge base on human genome epidemiology.

HuGENet Handbook of Systematic Reviews: The first edition of this handbook, published in 2006, provides guidelines, systematic review, and meta-analysis of gene disease association studies.

STrengthening the Reporting of Genetic Associations (STREGA): A workshop held in Canada in July 2006 engaged epidemiologists, geneticists, and journal editors in developing guidance for reporting research results in ways that promote knowledge synthesis (manuscript in preparation.)

Grading the Evidence for Genetic Associations: This workshop, held in Venice in 2006, produced draft guidelines that are being submitted for publication.

Current Activities

HuGE Navigator: OPHG will release completed components of HuGE Navigator suite, including HuGE Published Literature Finder, Investigator Browser, and Prediction Checker; continue development of other components, including HuGEpedia, which will summarize published evidence for gene-disease associations; publish manuscripts providing open source code for HuGE Navigator and describing applications. (First such article, which described the Investigator Browser, was published in June 2007.)

HuGE informatics: OPHG is developing customizable data mining tools for use by Network of Networks.

HuGENet^TM Meeting, January 24-25, 2008: OPHG is developing an agenda focused on further development of network approaches. This meeting will follow the OPHG 10th Anniversary meeting planned for January 23, 2007.

Human Genome Epidemiology, 2nd edition: OPHG is currently working on the first drafts of chapters, which are due in December 2007.

Next Steps

Pharmacogenomics: preliminary work is underway to characterize the published literature reporting pharmacogenomics research based on epidemiologic study designs; exploratory conversations are scheduled with PharmGKB. HuGENet may be able to help enrich the PharmGKB database.

Genetic testing: similar work is needed to characterize the published literature, especially on clinical validity. A pilot project is underway, comparing HuGE Pub Lit with EGAPP™ review of UGT1A1 testing for colorectal cancer treatment.

HuGENet challenges: respond to changing research landscape, especially genome-wide association studies. Find new ways to add value, e.g., via HuGEpedia and other approaches to “field synopses” proposed in 2006 “roadmap” article; reinforce international collaborations and broaden outreach from HuGENet to non-English-speaking world; and explore costs, benefits, and consequences of centralized vs. “distributed” (networked) data sharing. Establish collaboration with the National Library of Medicine (PubMed, dbGAP).

Selected Publications

1. Khoury MJ, Dorman JS. The Human Genome Epidemiology Network. Am J Epidemiol. 1998 Jul 1;148(1):1-3.
   
2. Ioannidis JP, Bernstein J, Boffetta P, et al. A network of investigator networks in human genome epidemiology. Am J Epidemiol. 2005 Aug 15;162(4):302-4.
   
3. Ioannidis JP, Gwinn M, Little J, et al. A road map for efficient and reliable human genome epidemiology. Nat Genet. 2006 Jan;38(1):3-5.
   
4. Little J, Higgins J. HuGENetTM HuGE Review Handbook, version 1.0 (Mar 2006). Web site. www.genesens.net/_intranet/doc_nouvelles/HuGE%20Review%20Handbook%20v11.pdf[PDF 166KB]
5. Lin BK, Clyne M, Walsh M, Gomez O, Yu W, Gwinn M, Khoury MJ. Tracking the epidemiology of human genes in the literature: the HuGE Published Literature database. Am J Epidemiol. 2006 Jul 1;164(1):1-4.
   
6. Khoury MJ, Little J, Higgins J, Ioannidis JP, Gwinn M. Reporting of systematic reviews: the challenge of genetic association studies. PLoS Med. 2007 Jun 26;4(6):e211
   
7. Yu W, Yesupriya A, Wulf A, Qu J, Gwinn M, Khoury MJ. An automatic method to generate domain-specific investigator networks using PubMed abstracts. BMC Med Inform Decis Mak. 2007 Jun 20;7(1):17