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 #
5U01HG004803-04
Application #
8112748
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
2011-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2011
Total Cost
$1,777,429
Indirect Cost
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
Gong, J; Nishimura, K K; Fernandez-Rhodes, L et al. (2018) Trans-ethnic analysis of metabochip data identifies two new loci associated with BMI. Int J Obes (Lond) 42:384-390
Kocarnik, Jonathan M; Richard, Melissa; Graff, Misa et al. (2018) Discovery, fine-mapping, and conditional analyses of genetic variants associated with C-reactive protein in multiethnic populations using the Metabochip in the Population Architecture using Genomics and Epidemiology (PAGE) study. Hum Mol Genet 27:2940-2953
Jo Hodonsky, Chani; Schurmann, Claudia; Schick, Ursula M et al. (2018) Generalization and fine mapping of red blood cell trait genetic associations to multi-ethnic populations: The PAGE Study. Am J Hematol :
Fernández-Rhodes, Lindsay; Malinowski, Jennifer R; Wang, Yujie et al. (2018) The genetic underpinnings of variation in ages at menarche and natural menopause among women from the multi-ethnic Population Architecture using Genomics and Epidemiology (PAGE) Study: A trans-ethnic meta-analysis. PLoS One 13:e0200486
Bien, Stephanie A; Pankow, James S; Haessler, Jeffrey et al. (2017) Transethnic insight into the genetics of glycaemic traits: fine-mapping results from the Population Architecture using Genomics and Epidemiology (PAGE) consortium. Diabetologia 60:2384-2398
Avery, Christy L; Wassel, Christina L; Richard, Melissa A et al. (2017) Fine mapping of QT interval regions in global populations refines previously identified QT interval loci and identifies signals unique to African and Hispanic descent populations. Heart Rhythm 14:572-580
Yoneyama, S; Yao, J; Guo, X et al. (2017) Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations. Int J Obes (Lond) 41:324-331
Fernández-Rhodes, Lindsay; Gong, Jian; Haessler, Jeffrey et al. (2017) Trans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci. Hum Genet 136:771-800
Zubair, Niha; Graff, Mariaelisa; Luis Ambite, Jose et al. (2016) Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci. Hum Mol Genet 25:5500-5512
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

Showing the most recent 10 out of 62 publications