Recently, consortia of genome-wide association studies (GWAS) have formed around specific phenotypes such as type 2 diabetes and lipids to identify associations with genetic variants. In contrast, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was formed in Feb 2008 to facilitate GWAS prospective meta-analyses of a wide range of phenotypes among large population-based cohort studies, including the Age, Gene/Environment Susceptibility Study, Atherosclerosis Risk in Communities Study, Cardiovascular Health Study, Framingham Heart Study, and the Rotterdam Study. The Health Aging and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Coronary Artery Risk Development in Young Adults Study are now participating as well. With more than 53,000 participants, these cohort studies have both genome-wide data and repeated measures of risk factors, subclinical disease measures, and cardiovascular events all collected in a standardized fashion. The CHARGE collaboration, which takes advantage of the hundreds of millions of dollars already invested in these cohort studies, represents a major innovation in consortium structure because the organizing principle is the cohort study design rather than the phenotype. In just over a year and a half of collaboration, the CHARGE investigators have 21 papers published or in press, 14 papers under review, and about 50 other analyses or papers in progress. The CHARGE consortium represents an unfunded voluntary federation of large complex studies, one that lacks infra-structural support to sustain its increasingly complex operations. The two functions that none of the cohorts can offer in a sustained way are: 1) administrative Coordinating-Center-like support for working groups, committees, conference calls, meetings, tracking publications, and upgrades to the website and wiki;and 2) modest genotyping resources for follow-up and replication efforts often required by editors and reviewers. In the proposed R01, we plan to provide not only Coordinating-Center support and modest genotyping resources, but also support for students, fellows and junior investigators, including new opportunities for junior investigators from one site to spend time working at another site (exchanges). Junior investigators have often taken a leading role in CHARGE analyses and manuscripts with the result that the CHARGE consortium has become a kind of de facto international training ground for collaborative epidemiological efforts in the genetics of aging and cardiovascular disease. All CHARGE papers have junior investigators among the set of investigators identified as contributing equally as first authors. First-first authors of CHARGE meta-analysis papers have frequently been doctoral students (n=4), post-doctoral fellows (n=2), or junior investigators (n=5). Support for students and junior investigators and support for between-cohort exchanges will foster collaboration, enhance the current science, and improve the training of our future scientists.

Public Health Relevance

The proposed project will assist in the discovery of genetic variants associated with a variety of cardiovascular and aging conditions. The findings may lead to a new understanding about a disease processes, prevention and treatment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL105756-02
Application #
8230469
Study Section
Cardiovascular and Sleep Epidemiology (CASE)
Program Officer
Papanicolaou, George
Project Start
2011-02-15
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2012
Total Cost
$668,917
Indirect Cost
$98,358
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Rao, D C; Sung, Yun J; Winkler, Thomas W et al. (2017) Multiancestry Study of Gene-Lifestyle Interactions for Cardiovascular Traits in 610 475 Individuals From 124 Cohorts: Design and Rationale. Circ Cardiovasc Genet 10:
Justice, Anne E (see original citation for additional authors) (2017) Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. Nat Commun 8:14977
Zillikens, M Carola; Demissie, Serkalem; Hsu, Yi-Hsiang et al. (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nat Commun 8:80
(2017) 19th Workshop of the International Stroke Genetics Consortium, April 28-29, 2016, Boston, Massachusetts, USA: 2016.001 MRI-defined cerebrovascular genomics-The CHARGE consortium. Neurol Genet 3:S2-S11
McLaughlin, Russell L; Schijven, Dick; van Rheenen, Wouter et al. (2017) Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. Nat Commun 8:14774
Joshi, Peter K; Pirastu, Nicola; Kentistou, Katherine A et al. (2017) Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nat Commun 8:910
Mozaffarian, Dariush; Dashti, Hassan S; Wojczynski, Mary K et al. (2017) Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts. PLoS One 12:e0186456
Ben-Avraham, Dan; Karasik, David; Verghese, Joe et al. (2017) The complex genetics of gait speed: genome-wide meta-analysis approach. Aging (Albany NY) 9:209-246
Hibar, Derrek P (see original citation for additional authors) (2017) Novel genetic loci associated with hippocampal volume. Nat Commun 8:13624
Smith, Caren E; Follis, Jack L; Dashti, Hassan S et al. (2017) Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent. Mol Nutr Food Res :

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