Genomic and bioinformatic approaches for understanding the effects of childhood adversity on primary tooth formation and caries development in young children

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Project Summary. This Short-Term Mentored Career Enhancement Award in Dental, Oral, and Craniofacial (DOC) Research for Mid-Career and Senior Investigators (K18) will provide the candidate with the protected time to acquire the skills and knowledge to augment her research program to include DOC concepts. The PI is an established investigator who studies the genetic, epigenetic, and social- environmental determinants of depression, with a focus on the role of childhood adversity in early life. The PI has not yet received any formal training in dental development nor any DOC concept. She seeks short-term training to learn concepts and methods to measure tooth development and dental hard tissue phenotypes, which she will then use to achieve her career goal of studying the connections between tooth and brain development. Training will be overseen by mentor Dr. Mary L. Marazita, an internationally recognized expert in the genetics of caries and other DOC features, along with three senior advisors. Training will consist of coursework, on-line seminars, guided readings, conference attendance, and lab experiences at two sites (University of Kent and Calgary), which will provide training distinct from the PI’s and mentor’s home institutions. Training will also include a secondary analysis of a study from the Center for Oral Health Research in Appalachia (COHRA). Under one of COHRA’s projects (R01-DE014899 PD/PIs Marazita, McNeil, Foxman, Shaffer) the COHRA2 longitudinal birth cohort was built and followed 1000 European-ancestry and 250 African American pregnant women from northern Appalachia. The PI will analyze existing data from COHRA2 to investigate the extent to which genetic factors and children’s exposure to maternal distress, a common type of childhood adversity, associate with dental caries (tooth decay) and age at first tooth eruption. In Aim 1, the PI will use bioinformatics data on brain structures and disorders to calculate genetic risk scores capturing the aggregate effect of multiple genes (i.e., polygenic risk scores; PRS) and then examine their role on both dental caries risk and age at first tooth emergence. In Aim 2, the PI will use an analytic technique called the structured lifecourse modeling approach (SLCMA) to assess with repeated-measures data how the developmental timing of children’s exposure to maternal distress (e.g., global and parenting stress; depressive symptoms) associates with number of dental caries and primary tooth eruption timing. Findings from this K18 may lead to the identification of new genes associated with dental caries and tooth formation timing, and increase knowledge on the role of maternal distress on these dental outcomes, which could then guide targeted preventive interventions. The proposed training experiences will ensure the PI learns concepts and measurement approaches to study tooth formation so she can more deeply integrate these concepts into her research. This K18 will also serve as the basis for an R01 proposal that will replicate and extend findings investigated here.