The Fragile Families Cardiovascular Health Follow Up Study

心血管疾病（CVD）仍然是死亡和残疾的主要原因， 美国的成年人。CVD及其风险因素不成比例地影响少数民族和较低的社会经济地位 (SES)美国人在治疗CVD和控制某些心脏代谢风险方面取得了重大进展 目前，研究人员已经发现了一些重要的CRF因素，但包括肥胖和糖尿病在内的关键CRF的患病率增加可能会限制未来的进展。 关于心血管疾病的社会决定因素及其可能影响心血管疾病发展轨迹的机制知之甚少。 CRF和CVD。CVD的遗传、环境、行为和社会决定因素之间的相互作用尚未得到证实。 由于缺乏从出生到成年的大量不同群体的高质量数据，对这一问题进行了深入研究。 自2000年以来，脆弱家庭和儿童福利研究（FFCWS）提供了社会科学 一个社区拥有近5000名在大城市出生的美国儿童的纵向出生队列数据， 从出生起就被多次调查FFCWS包含大量的种族和少数民族：47% 黑人儿童，27%的西班牙裔儿童（17%的儿童出生于移民西班牙裔父母）。约40%的 这些家庭生活在贫困线以下。除了社会经济、人口统计、邻里关系和 发育数据，我们的团队已经开发了一个大型的儿童遗传和表观遗传数据组合， 参与者这些特征使数据在其他大规模纵向研究中独一无二，因此很好地- 适用于研究脆弱年轻人心血管健康（CVH）的社会决定因素。 我们建议将这些生物学和社会科学数据与新获得的CVH指标联系起来，包括， 其中包括：血浆生物标志物、拟人测量、健康相关行为和颈动脉 超声.我们计划将大型FFCWS年轻成年人队列从出生到 青少年，进入健康的社会决定因素（SDoH）及其对CVH的影响的纵向研究。 我们将进行创新的亲自检查，以测量CVH的所有组成部分和早期证据 亚临床心血管疾病（CVD）我们的总体目标是了解早期生活逆境的作用 在CVH和CVD的演变中，以及潜在的表观遗传介导。我们的建议发展为三个 目标1：我们将测试早期生活SDoH的关联（见表1，研究计划） 在FFCWS中收集总体CVH状态（14分量表）和CVH的7个特定指标中的每一个， 年龄约22岁（N=2400）。目标2：我们将评估早期生活SDoH与存在 在FFCWS的子样本中通过颈动脉超声确定年轻成人亚临床CVD的程度（n~1800）。 目的3：我们将：a）检查表观遗传措施（DNA甲基化，DNAm，在9，15， 和22岁）的上游早期生命SDoH和下游年轻成人CVH和亚临床CVD; B）探索 DNAm对早期生活SDoH和年轻成人CVH之间已发现的关联的潜在介导作用， 亚临床CVD，解释了与CVH和亚临床CVD相关的已知遗传效应。

Project Summary: Cardiovascular disease (CVD) remains the leading cause of death and disability for adults in the US. CVD and its risk factors disproportionately affect minorities and lower socioeconomic status (SES) Americans. Major strides have been made in treatment of CVD and control of some cardiometabolic risk factors (CRFs), but increasing prevalence of key CRFs, including obesity and diabetes, may limit future progress. Little is known about social determinants of CVD and mechanisms by which they may influence trajectories of CRFs and CVD. The interplay of genetic, environmental, behavioral and social determinants of CVD has not been well studied, due to lack of high-quality data in large diverse groups followed from birth to young adulthood. Since 2000, the Fragile Families and Child Wellbeing Study (FFCWS) has provided the social science community with data on a longitudinal birth cohort of nearly 5000 American children born in large cities and surveyed in multiple waves since birth. FFCWS contains a large number of racial and ethnic minorities: 47% Black children, 27% Hispanic children (17% children born to immigrant Hispanic parents). Approximately 40% of the families live below the poverty line. In addition to socioeconomic, demographic, neighborhood, and developmental data, our team has developed a large portfolio of genetic and epigenetic data for child participants. These features make the data unique among other large-scale, longitudinal studies, and thus well- suited for studying social determinants of the cardiovascular health (CVH) of vulnerable young adults. We propose to link this biologic and social science data with newly acquired measures of CVH including, among others: plasma biomarkers, anthropomorphic measurements, health-related behavior, and carotid ultrasound. We plan to transition the large FFCWS cohort of young adults, followed from birth through adolescence, into a longitudinal study of social determinants of health (SDoH) and their influence on CVH. We will perform an innovative in-person examination to measure all components of CVH and early evidence of subclinical cardiovascular disease (CVD). Our over-arching goal is to understand the role of early life adversity in the evolution of CVH and CVD, and potential epigenetic mediation. Our proposal is developed into three cohesive and interlocking aims: Aim 1: We will test associations of early life SDoH (see Table 1, Research Plan) collected in FFCWS with overall CVH status (14-point scale) and each of the 7 specific metrics of CVH, at approximately age 22 years (N=2400). Aim 2: We will assess associations of early life SDoH with the presence and extent of young adult subclinical CVD determined by carotid ultrasound in a subsample of FFCWS (n~1800). Aim 3: We will: a) examine temporal associations of epigenetic measures (DNA methylation, DNAm, at 9, 15, and 22 years) with upstream early life SDoH and downstream young adult CVH and subclinical CVD; b) explore potential mediation by DNAm of the discovered associations between early life SDoH and young adult CVH and subclinical CVD, accounting for known genetic effects on associations with CVH and subclinical CVD.