Genetic Epidemiology of Causal Variants Across the Life Course is submitted in response to RFA HG-07-014, as a consortium of well characterized population based studies and a central genotyping and resequencing core laboratory, to accelerate the understanding of the role and population impact of putative causal genetic variants related to complex diseases. This collaborative network includes six of the most informative and demographically diverse population-based studies extant, contributing approximately 58,000 men and women from the main ethnic and racial groups in the U.S., ranging in age from childhood to old adulthood. Those examined in the six studies are extensively characterized for a wide range of phenotypes and traits, and five studies have immediately available stored DNA of high quality for transfer to the core laboratory. The participating studies include population based cohorts with repeat examinations and long term follow up and a national probability sample, with clinical and subclinical measurements on a range of health conditions, their precursors and natural history, characterized across the life course. This collaborative network is designed to provide optimal capabilities to estimate and replicate associations of genetic variants with complex diseases in diverse U.S. populations, in individual and environmental contexts of public health relevance, with power sufficient to identify associations, interactions, and population impact in subgroups. The team of investigators contributes epidemiologic, genetic, methodologic and subject-matter expertise and a demonstrated record of productivity in collaborative, interdisciplinary settings. The network builds on existing capabilities and the proven administrative channels of the assembled partner studies for efficient and timely access to phenotypic, exposure and contextual data, for analyses within each partner study and for replication across studies, and for rapid sharing of the resulting descriptive and association data. The investigators will serve as effective collaborators within the wider study, contributing methodologic innovation and analytic support and serving on committees and working groups set up by the Steering Committee. The collaborative resource assembled in this application will permit the estimation of the role and population impact of selected genetic variants in diversity-based populations, for an array of chronic diseases, their risk factors and intermediate outcomes, at different life epochs, and for groups defined by potentially modifiable contexts. Genomic assays will be conducted as needed to further characterize the reported associations.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project--Cooperative Agreements (U01)
Project #
3U01HG004803-04S1
Application #
8443562
Study Section
Special Emphasis Panel (ZHG1-HGR-M (M1))
Program Officer
Hindorff, Lucia
Project Start
2008-07-17
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$980,292
Indirect Cost
$161,496
Name
University of North Carolina Chapel Hill
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Kocarnik, Jonathan M; Park, S Lani; Han, Jiali et al. (2015) Pleiotropic and sex-specific effects of cancer GWAS SNPs on melanoma risk in the population architecture using genomics and epidemiology (PAGE) study. PLoS One 10:e0120491
Mou, Zongyang; Hyde, Thomas M; Lipska, Barbara K et al. (2015) Human Obesity Associated with an Intronic SNP in the Brain-Derived Neurotrophic Factor Locus. Cell Rep 13:1073-80
Carty, Cara L; Bhattacharjee, Samsiddhi; Haessler, Jeff et al. (2014) Analysis of metabolic syndrome components in >15 000 african americans identifies pleiotropic variants: results from the population architecture using genomics and epidemiology study. Circ Cardiovasc Genet 7:505-13
Kocarnik, Jonathan M; Pendergrass, Sarah A; Carty, Cara L et al. (2014) Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study. Circ Cardiovasc Genet 7:178-88
Lim, Unhee; Kocarnik, Jonathan M; Bush, William S et al. (2014) Pleiotropy of cancer susceptibility variants on the risk of non-Hodgkin lymphoma: the PAGE consortium. PLoS One 9:e89791
Seyerle, Amanda A; Young, Alicia M; Jeff, Janina M et al. (2014) Evidence of heterogeneity by race/ethnicity in genetic determinants of QT interval. Epidemiology 25:790-8
Park, S Lani; Fesinmeyer, Megan D; Timofeeva, Maria et al. (2014) Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: the PAGE and TRICL consortia. J Natl Cancer Inst 106:dju061
Setiawan, Veronica Wendy; Schumacher, Fredrick; Prescott, Jennifer et al. (2014) Cross-cancer pleiotropic analysis of endometrial cancer: PAGE and E2C2 consortia. Carcinogenesis 35:2068-73
Cheng, Iona; Kocarnik, Jonathan M; Dumitrescu, Logan et al. (2014) Pleiotropic effects of genetic risk variants for other cancers on colorectal cancer risk: PAGE, GECCO and CCFR consortia. Gut 63:800-7
Lin, Dan-Yu; Tao, Ran; Kalsbeek, William D et al. (2014) Genetic association analysis under complex survey sampling: the Hispanic Community Health Study/Study of Latinos. Am J Hum Genet 95:675-88

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