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

基因组和生物信息学方法用于了解童年逆境对幼儿乳牙形成和龋齿发展的影响

• 批准号: 10739519
• 负责人: Erin Cathleen Dunn
• 金额: $ 17.33万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2024-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10739519
• 关键词: Address; Affect; African American; Age; Anxiety; Appalachian Region; Award; Bioinformatics; Biological; Biological Process; Birth; Brain; Child; Child Rearing; Data; Dedications; Dental; Dental caries; Development; Dimensions; Disease; Distress; Ensure; Environmental Health; Environmental Risk Factor; Epidemiologist; Epigenetic Process; European ancestry; Event; Exposure to; Family; Generations; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Genomics; Goals; Health; Home; Individual; Institution; International; Intervention; K-18 conjugate; Knowledge; Learning; Life; Life Cycle Stages; Longevity; Longitudinal Studies; Measurement; Measures; Mental Depression; Mentors; Methods; Modeling; Mothers; National Institute of Dental and Craniofacial Research; Nursery Schools; Odontogenesis; Oral; Oral health; Outcome; Pathway interactions; Phenotype; Pregnancy; Pregnant Women; Process; Reporting; Research; Research Personnel; Research Training; Risk; Risk Factors; Role; Shapes; Site; Statistical Methods; Strategic Planning; Stress; Structure; Techniques; Technology; Testing; Time; Tissues; Tooth Exfoliation; Tooth eruption; Tooth structure; Training; United States; Universities; Work; Youth; bioinformatics tool; brain based; career; childhood adversity; cohort; craniofacial; deciduous tooth; depressive symptoms; epidemiology study; experience; genetic variant; genome wide association study; genome-wide; health data; infancy; insight; interest; laboratory experience; low socioeconomic status; material transfer agreement; middle childhood; novel; offspring; peer; polygenic risk score; preventive intervention; programs; prospective; research study; secondary analysis; skill acquisition; skills; social; social factors; sociodemographic factors; stressor; symposium; translational genomics

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.

该项目摘要是牙科、口腔和口腔领域的短期指导职业提升奖。 职业中期和高级研究人员的颅面 (DOC) 研究 (K18) 将为候选人提供 用受保护的时间来获得技能和知识，以扩大她的研究计划，包括 DOC 概念。 PI 是一位研究遗传、表观遗传和社会学的资深研究者。 抑郁症的环境决定因素，重点关注童年逆境在早年生活中的作用。 PI 尚未接受过任何牙科发育方面的正式培训，也没有接受过任何 DOC 概念。 短期培训学习测量牙齿发育和牙齿硬组织的概念和方法 表型，然后她将用它来实现她的职业目标，即研究之间的联系 牙齿和大脑的发育将由国际知名导师 Mary L. Marazita 博士监督。 龋齿遗传学和其他 DOC 特征领域公认的专家，以及三名高级顾问。 培训将包括课程作业、在线研讨会、指导阅读、参加会议和实验室 在两个地点（肯特大学和卡尔加里大学）的经验，这将提供与 PI 不同的培训 培训还将包括对中心研究的二次分析。 阿巴拉契亚口腔健康研究 (COHRA) 属于 COHRA 项目之一 (R01-DE014899)。 PD/PI Marazita、McNeil、Foxman、Shaffer）建立并跟踪了 COHRA2 纵向出生队列 来自阿巴拉契亚北部的 1000 名欧洲血统孕妇和 250 名非裔美国孕妇。 将分析 COHRA2 的现有数据，以调查遗传因素和儿童的影响程度 遭受母亲的痛苦，这是一种常见的童年逆境，与龋齿（牙齿）有关 在目标 1 中，PI 将使用有关大脑结构和年龄的生物信息学数据。 疾病来计算遗传风险评分，捕捉多个基因的总体效应（即多基因 风险评分；PRS），然后检查它们对龋齿风险和首次牙齿萌出年龄的作用。 在目标 2 中，PI 将使用一种称为结构化生命历程建模方法的分析技术 （SLCMA）通过重复测量数据评估儿童接触的发育时间如何 孕产妇痛苦（例如，整体压力和养育压力；抑郁症状）与产妇数量相关 K18 的发现可能有助于识别龋齿和乳牙萌出时间。 与龋齿和牙齿形成时间相关的新基因，并增加对其作用的了解 孕产妇对这些牙科结果的痛苦，这可以指导有针对性的预防干预措施。 拟议的培训经验将确保 PI 学习概念和测量方法 研究牙齿形成，以便她可以更深入地将这些概念融入到她的研究中。 也作为 R01 提案的基础，该提案将复制和扩展此处调查的结果。