Sex- and Smoking- Specific DNA Methylation Signatures of Central Adiposity Change

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 DESCRIPTION (provided by applicant): ABSTRACT Candidate: This is a NHLBI K99/R00 grant proposal, intended to promote my career as a post-doctoral fellow at the University of North Carolina, into independence as a genetic epidemiologist with a focus in obesity epigenetics. I am a trained anthropological geneticist with extensive experience in genetic epidemiology and a strong track record of innovative and informative research. Research and Career Goals: My over-arching research goal is to integrate my skills as an anthropologist, population geneticist, and epidemiologist, using the bio-cultural and public health perspectives to identify genetic, epigenetic and environmental factors that influence obesity and downstream cardiometabolic disease (CMD) across the lifecourse. Related to this, my long-term career goals include securing a faculty position at a research university where I will continue my research on the genetic and environmental factors that influence risk of CMD as an independent researcher and educator. Career Development: I will develop: 1) expertise in the pathogenesis of obesity, 2) a strong foundation in longitudinal data analysis, and 3) the theoretical and analytical skills specific for epigenetics research. My training and proposed research will be overseen by a talented group of mentors, including my primary mentor, Kari North, a renowned genetic epidemiologist that will provide expertise in integrating genetics and epigenetic analysis and methods; and my co-mentors, Penny Gordon-Larsen, a nutritionist and internationally recognized obesity expert; Yun Li, a biostatistician and geneticist with expertise in the development and application of analytical methods for genetics and epigenetics; Annie Green Howard, a biostatistician that specializes in longitudinal data analysis; Ellen Demerath, consultant, a lifecourse CMD epidemiologist with experience in methylation research; and Eric Whitsel, collaborator, a CVD epidemiologist and physician with experience in pharmacogenomics. Research Project: The proposed project aims to identify methylation variants (meQTLs) associated with increased central adiposity and for which the effects may be influenced by environmental exposures (sex, obesogenic medications, smoking) in the African American participants of the Atherosclerosis Risk in Communities (ARIC) study. In the K99 phase, I will conduct an epigenome wide association analysis (EWAS) with central adiposity using methylation data from a single time point and while accounting for environmental exposures. During the R00 phase, I will collect de novo methylation data using stored biospecimens from visit five to implement longitudinal, multilevel, and mixed models to examine differential epigenetic effects on central adiposity by age and time, and to examine the causal relationships between central adiposity change, methylation, and environmental exposures. Projects, like that proposed herein, allow us to identify epigenetic variation that influences central adiposity, and are critical to gain a comprehensive understanding of the pathogenesis of obesity. The results of this study and the continued protected training time will ultimately launch my career in lifecourse obesity epigenetics.