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NHANES III DNA Bank
- National Health and Nutrition Examination Survey
(NHANES) is a nationally representative survey
- Detailed interviews, clinical, laboratory and
radiologic examinations are conducted
- Phenotypic data, such as serostatus for many
infectious exposures, blood count, chemistries,
etc. were collected
- During second phase NHANES III (1991-1994),
white blood cells were frozen and cell lines
were immortalized with EBV
- NHANES III DNA bank is located at NCEH,CDC,
with specimens available from over 7000 participants
- In 2002, NCHS announced a call for proposals to
use these specimens in the Federal Register
| Collaborative CDC-wide Proposal Objective |
- Determine the prevalence of genotypes of public health
importance.
| Criteria for Genetic Variants |
Public Health Importance
- Known or hypothesized association with diseases of
public health importance
- Role in pathways affecting multiple diseases
Identified functional variants
- Relatively common (i.e., >2.0%)
- Previously described gene-environment or gene-gene interactions
- Relevant phenotypic data available in NHANES dataset
- No current use for clinical risk assessment or intervention
| Challenges to Identifying Genes of Public Health Importance |
- Gaps in information in the literature
- Methodological issues of many available studies
- Selection bias, power, interaction
- Non-replication of gene-disease association
| Public Health Significance of Proposal |
- Prevalence of gene variants
- Basis for estimating population attributable fraction in
combination with measure of gene-disease association
- Enable assessment of potential for screening population
subgroups for susceptibility genes
- Prevalence of combinations of variants in pathways
and at different loci
- Examine gene-disease association, gene-environment
and gene-gene interactions
| Selected Pathways of Gene Variants |
(87 variants of 57 genes)
- Nutrient Metabolism (e.g., folate and homocysteine; lipids; glucose; alcohol; vitamin D)
- Immune and Inflammatory responses (e.g., cytokines, receptors)
- Activation and detoxification pathways (e.g., drugs, carcinogens, environmental contaminants)
- DNA repair pathways (e.g. ionizing radiation, environmental toxins)
- Hemostasis pathway and renin/angiotension (e.g. vasomotor) pathway
- Developmental (e.g., hearing loss)
- Genotyping
- Assessing Capability of External Laboratories to conduct high
throughput, accurate, low-cost, genotyping for >600,000 SNPs
(~7300 specimens X 87 variants*)
*Table of gene variants available upon request
- Pending approval from NCHS:
- Laboratory Selected
- Genotype-Phenotype analyses
ATSDR Olivia Harris NCBDDD Karen Abe, Cynthia Moore, Lorenzo Botto, Quanhe Yang NCHSTP Mary Reichler NCID Tom Hodge, Craig Hooper, Jai Lingappa, Janet McNicoll, Anne Dilley
NCEH Amanda Brown, Peg Gallagher, Marta Gwinn, Omar Henderson, Bruce Lin, Mary Lou Lindegren, Julian
Little, Karen Steinberg
NCCDPHP Heidi Blanck, Wayne Giles, Ingrid Hall, Giuseppina Imperatore, Ann Malarcher NIOSH MaryAnn Butler, Ainsley Weston PHPPO Bin Chen NIP Scott Campbell NCHS Gerry McQuillan
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