Poster #77 - Eve Schoeffler

Emergent patterns of methylation across early life associated with carotid intima-media thickness in young adults

Eve Schoeffler a+, Lisa M. Schneper a+, Yinan Zheng b, Mindy Szeto b, Shantelle Little a, Ayanava Ganguly a, Hongyan Ning b, Colter Mitchell e, Boriana P. Pratt d, Jun Wang b,f, Claudia Korcarz c, Kristin Hansen c, Nicole Katchur a, Elisabeth Tawa a, Lifang Hou b,f, Jim Stein c, Norrina Bai Allen b, Noreen Goldman d, Donald M. Lloyd-Jones b,g+, Daniel A. Notterman a+* +ES and LS contributed equally, DLJ and DN contributed equally * To whom correspondence should be addressed: dan1@princeton.edu a Department of Molecular Biology, Princeton University, Princeton NJ, USA b Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago IL, USA c University of Wisconsin Atherosclerosis Imaging Research Program, Section of Cardiovascular Medicine, University of Wisconsin Medical School, Madison, WI, USA d Office of Population Research and School of Public and International Affairs, Princeton University, Princeton NJ, USA e Population Studies Center, Institute for Social Research, University of Michigan, Ann Arbor MI, USA f The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA g Framingham Center for Population & Prevention Research and Section of Preventive Medicine Epidemiology, Boston University School of Medicine, Boston, MA

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality and usually manifests clinically later in life, although risk factors are known to emerge during childhood and adolescence. In a longitudinal assessment, we examined whether DNA methylation in childhood, adolescence, and young adulthood could act as a potential biomarker for carotid intima-media thickness (CIMT) in young adulthood, at 22-23 years of age. DNA methylation data from participants in The Future of Families and Child Wellbeing Study (FFCWS) at approximately nine, 15, and 22 years of age were associated with their carotid intima-medial thickness (CIMT) through epigenome-wide association studies (EWAS), differentially methylated region (DMR) analysis, and functional enrichment analysis. Genes previously associated with epithelial function, vascular development, and hypertension were implicated by nine years, indicating that the cascade of events that lead to later atherosclerosis can be detected relatively early in childhood. Predictive methylation profiles from young ages may provide mechanistic insight into the pathogenesis of atherosclerosis and inform future interventions.