The Epidemiology and Genetics (E&G) Core provides a central focus to translate the findings from clinical and cellular studies to applications in ongoing epidemiologic studies. The Core fosters new epidemiologic initiatives that draw on the clinical and biologic developments from other components of the BNORC. Further, the Core provides a center for training and development of expertise among statisticians who provide consultation to other studies within the BNORC. In contrast with other cores, the E&G Core provides most of its services through consultation and analysis of data sets. It provides consultation on study design, on the analytic approaches to data from clinical trials and epidemiologic and genetic studies, and the presentation of results. To provide these services, the core conducts a regular working group in obesity research where data plans, preliminary analyses, and research results are presented. Core faculty also meets one-on-one with researchers. Programming support is also provided to studies lacking the necessary expertise. In the last competing renewal, we expanded the core services to include genetic epidemiology and statistical analysis of obesity and related phenotypes. These services have contributed to the discovery of genetic variants for the common form of obesity through genome-wide association studies (GWAS). To date, more than 50 genetic loci have been convincingly associated with obesity. These discoveries have substantially enhanced our understanding of the pathophysiology of energy balance and obesity and have provided potential new targets for obesity prevention and treatment. However, these loci confer only a modest effect size and do not add to the clinical prediction of obesity. There is increasing evidence that epigenetic regulation of gene expression may contribute to an individual's predisposition to obesity and its related chronic diseases and may also explain part of the 'missing heritability'. In particular, fetal undernutrition has been associated with increased risk of obesity and diabetes and these effects are likely to be mediated by DNA methylation due to intrauterine or earty childhood exposures rather than changes in genotypes. To address this challenge, we propose in this renewal application to expand the core's services by expanding the pool of longitudinal datasets available and the core faculty expertise (Dr. Chavarro -nutntion and reproductive epidemiology- and Dr. Baccarelli -epigenetics) in order to facilitate research aimed at identifying epigenetic contnbutions to the developmental ongins of obesity and its related phenotypes. The E&G Core builds on the large cohorts of men and women that have been established to relate lifestyle factors, including diet, anthropometric characteristics, and exercise, to the incidence of major illnesses and subsequent mortality. These cohorts include the Health Professionals Follow-up Study (HPFS), the Nurses' Health Study (NHS), the NHS II, and the Growing Up Today Study (GUTS), a cohort of adolescents and young adults (based at Harvard School of Public Health and Brigham and Women's Hospital). New cohorts that will be made available through the BNORC include the NHS 3 and the nutritional component of the EARTH Study (based at MGH). Additional cohort studies that are available to core members include the Framingham Heart Study (based at Boston University), the Boston Puerto Rican Health Study (based at Tufts University and Northeastern University), and the Black Women's Health Study (based at Boston University). The investigators have developed analytic and data management software to facilitate the analysis of large volumes of information in a cost-effective manner. In addition, these cohort studies have collected more than 200,000 plasma and 300,000 DNA samples for biomarker and genetic analyses.
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