Fiscal Year 2006
CDC’s Office of Genomics and Disease Prevention (NOPHG) in March 2006 announced the availability of seed funding for innovative CDC projects that integrate genomics into public health research and programs. Thirty-two proposals were received and eleven were selected, with priority given to those with potential to demonstrate health impact within two years. The following list provides information about 2006 seed funding recipients.
| Escherichia coli O157:H7 and other Shiga toxin-producing enterohemorrhagic E. coli (STEC)are estimated to cause over 110,000 illnesses, 3000 hospitalizations, and 90 mdeaths each year in the U.S. Approximately 8% of persons infected with E. coli O157 develop hemolytic-uremic syndrome (HUS). HUS is associated with substantial morbidity and mortality, with case fatality rates as high as 5%; HUS is the leading cause of renal failure in children. This project will apply genomic methods to determine host factors associated with HUS within a large, population-based cohort study persons infected with STEC. |
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| Diisocyanates are the most common cause of occupational asthma from low-molecular weight chemicals, still causing disease in 5-15 % of chronically exposed workers despite improved industrial hygiene efforts. With the recent development of genotype microarrays we are now capable of rapidly examining a large number of variants in the highly relevant MHC region in a case-control study of exposed workers. The results could be used to assess the genetic contribution in the risk of OA, identify the most susceptible (genetic) populations and apply relevant information to the risk assessment process by determining safe exposure levels for the most susceptible groups of workers. |
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| Gastroschisis and anorectal atresia/stenosis are two common, major birth defects. Gastroschisis, a herniation of the intestines through a defect in the abdominal wall, affects approximately 3.7 infants per 10,000 US births; anorectal atresia/stenosis, the congenital absence or narrowing of the anal or rectal canal, affects approximately 4.8 infants per 10,000 US births. Both of these birth defects are believed to have a multifactorial etiology including both environmental and genetic risk factors. Because some studies have reported maternal smoking as a risk factor for both defects, this case-control study will focus on potential interaction of maternal smoking with genes involved in metabolizing tobacco smoke (CYP2A6, CYP2B6, CYP2D6, CYP1A1, CYP1A2, CYP2E1, GSTT1, NAT1, and NAT2). |
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| Tuberculosis continues to be a major global health problem. Each year 54 million people worldwide are infected with Mycobacterium tuberculosis, 8.8 million develop clinical disease, and 1.75 million die of tuberculosis. In 1999, CDC’s Division of Tuberculosis Elimination launched a prospective multi-site study of epidemiologic, immunologic, and immunogenetic correlates of susceptibility to TB among contacts of infectious TB patients in a U.S. and Canadian-born study population. A total of 1,947 contacts have been enrolled in the study to date, with a total planned enrollment of 2,500. Specimens are being tested for three cytokine surrogate markers, HLA, and a dozen candidate gene single nucleotide polymorphisms (SNPs). This proposal seeks to 1) strengthen laboratory capacity, expanding testing from 18 candidate gene SNPs to all 33 SNPs with demonstrated associations with tuberculosis or strong biologic plausibility, and 2) to build specialized capacity to perform complex analyses, including haplotype analysis, while carefully evaluating multiple potential gene-gene and gene-environment interactions. |
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| Malaria is a major global public health problem, currently estimated to cause 300-500 million clinical cases and 1.1-2.7 million deaths annually throughout the world. Sub-Saharan Africa (SSA) accounts for 90% of all these cases and the disease exerts an adverse impact on the health of young children, pregnant women and their unborn infants. Previous studies conducted in Kenya, a malaria holoendemic and HIV epidemic area, have shown that gene polymorphism of the Fc receptor IIa for Ig (FcgRIIa), which determines differential affinity for human IgG subclasses, is associated with 1) high density malaria infection in children, 2) malaria infection in HIV positive women, and 3) perinatal HIV infection. The specific objectives of the proposed study are 1) to determine the association between Ig GM/ KM gene polymorphisms and malaria morbidity, including severe anemia, and mortality in children, 2) to determine the association of gene polymorphisms of Ig GM/ KM with outcomes of malaria infection in pregnant women, including maternal anemia, birth defects, and vertical transmission of HIV, 3) to determine the effects of Ig GM/ KM gene polymorphisms on the interaction between malaria and HIV-1 infection during pregnancy, and 4) to determine the differential interaction between Ig GM gene haplotype profiles and FcgRIIa genotypes and acquired antibody responses in relation to the above epidemiological and clinical parameters. |
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| Type 2 diabetes is a growing national health problem because of its rapidly increasing incidence and associated health impacts, including premature mortality, disabling sequelae, and risk of birth defects in offspring. Family history has been shown to be a strong predictor of diabetes risk, which could reflect both genetic risk and shared behaviors or environment. This project will develop a decision analytic and cost-effectiveness model to assess the likely outcomes of health promotion efforts that focus on the use of family history information on type 2 diabetes. The two specific aims are: 1) to develop a decision analytic and cost-effectiveness model to assess the effects on health outcomes and costs of health promotion efforts that focus on the use of family history of diabetes; and 2) to use this decision model to assess the effects of targeting health promotion efforts based on family history of diabetes on the outcomes and costs of: i) individuals with a family history of diabetes, ii) individuals without a family history of diabetes, and iii) the overall population of individuals. |
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| Warfarin is a common, chronically administered oral anticoagulant; 16 million prescriptions were dispensed in 2004. Warfarin reduces the risk of thromboembolic events by 50-79% in atrial fibrillation (AF) patients, yet is prescribed for only about half of the 2 million patients diagnosed with AF in the US each year, due in part to concerns about the risk of major bleeding and the challenges of closely monitoring and adjusting warfarin therapy. Recently, variants in the CYP2C9 and VKORC1 genes have been shown to significantly influence warfarin dose requirements, and in the case of CYP2C9, the risk of major bleeds. The use of CYP2C9 and VKORC1 genetic testing has thus been proposed to help guide warfarin therapy. Although the analytic and clinical validity of these associations has been established, their clinical utility is just beginning to be evaluated. This project will develop a disease-based simulation model and perform a cost-utility analysis from multiple stakeholder perspectives to help inform treatment decisions and guidelines and reimbursement policies. |
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| Abnormalities in the metabolism of folate and homocysteine are associated with cardiovascular disease and other conditions that contribute significantly to morbidity and mortality in the United States. Recently, researchers have identified several common polymorphisms of genes related to folate and homocysteine metabolism, including the C677T and the A1298C alleles of 5,10 methylenetetrahydrofolate reductase (MTHFR), the 844ins68 allele of cystathionine-beta-synthase (CBS), and the A66G allele of methionine synthase reductase (MTRR). These genetic variants may influence folate metabolism and disease risk, and that some of their effects may be mediated by gene-gene and gene-environment interactions. This study will assess whether the effect of folic acid intake on the blood levels of folate and homocysteine varies by genotype of folate-related genes, using data and DNA samples from NHANES III. |
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| CDC supports a collaborative study set in primary care clinics to determine whether family history risk assessment and classification using the Family Healthware™ (FHW) tool--an interactive web-based tool that collects information on personal health behaviors, screening, and family health history and offers personalized prevention messages--can influence health behaviors and the use of preventive medical services. This project will assess provider and consumer receptivity to the use of the Family Healthware™ (FHW) tool among providers in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), the Division of Cancer’s Colorectal Cancer (CRC) demonstration project, and the CDC-funded WISEWOMAN programs. Outcomes from this proposal will be used to inform research on expanding use of FHW into community health settings. |
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| Severe Combined Immunodeficiency Disorder (SCID) is a group of genetic conditions characterized by profound defects in both cellular and humoral immunity. Caused by the nearly complete failure to develop functional T-cells, SCID leads to severe bacterial and viral infections; without treatment, affected infants usually die within a year of birth. NIH and CDC have developed assays to detect profound T-cell lymphocytopenia by testing dried blood spots. Both assays use realtime PCR to measure T-cell recombination excision circles (TREC), the episomal circular DNA that is excised from T-cells when their V-genes recombine with the constant region genes of the T-cell receptor. The goals of this proposal are: 1) to establish authoritative methods for the standardization of the TREC assay to foster its systematic translation to public health newborn screening; 2) to determine the extent to which SCID contributes to early childhood mortality; and 3) to establish an ongoing partnership with the Newborn Screening Program in the California Department of Health Services to facilitate the investigation of other occult contributors to early childhood mortality. |
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| Osteoporosis is a major cause of morbidity in the elderly. Inherited factors are important determinants of peak bone mass, although the influence of genetic factors on bone turnover and changes in bone mass with aging is less clear. Over the past 20 years, several candidate genes have been associated bone mineral density (BMD); however, most studies have been conducted on relatively small convenience samples and few have examined the role of candidate genes on bone loss or fracture occurrence. This study will help fill these gaps by examining the relationship between these endpoints and two candidate genes (low-density lipoprotein -receptor related protein 5 (LRP5) gene (6), and the 116 T/G (Ser37Ala) polymorphism of the bone morphogenetic protein 2 (BMP2) gene (7) in a very large, community-based sample. The study takes advantage of an existing relationship with Kaiser Permanente San Diego. |
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