The Fragile Families Cardiovascular Health Follow Up Study

项目摘要：心血管疾病(CVD)仍然是#年死亡和残疾的主要原因 美国的成年人。心血管疾病及其风险因素对少数群体的影响不成比例，社会经济地位较低 (S)美国人。在治疗心血管疾病和控制某些心脏代谢风险方面取得了重大进展 影响因素(CRF)，但包括肥胖和糖尿病在内的关键CRF的患病率不断增加，可能会限制未来的进展。 关于心血管疾病的社会决定因素以及它们可能影响心血管疾病轨迹的机制，人们知之甚少 慢性肾功能衰竭和心血管疾病。心血管疾病的遗传、环境、行为和社会决定因素之间的相互作用尚未 由于缺乏从出生到成年的大量不同群体的高质量数据，这一问题得到了很好的研究。 自2000年以来，脆弱家庭和儿童福祉研究(FFCWS)提供了社会科学 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 从出生起就经历了多波调查。FFCWS包含大量种族和少数民族：47% 黑人儿童，27%是西班牙裔儿童(17%是西班牙裔移民父母所生的儿童)。约40%的 这些家庭生活在贫困线以下。除了社会经济、人口、社区和 发育数据，我们的团队开发了大量儿童的遗传和表观遗传学数据 参与者。这些特征使得这些数据在其他大规模的纵向研究中是独一无二的，因此 适合研究易受伤害的年轻人心血管健康(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：血浆生物标记物、拟人化测量、健康相关行为和颈动脉 超音波。我们计划将FFCWS庞大的年轻人队列从出生一直持续到 对健康的社会决定因素(SDoH)及其对CVH的影响的纵向研究。 我们将进行创新的面对面检查，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)。我们的首要目标是理解早年生活中的逆境所起的作用 在CVH和CVD的演变中，以及潜在的表观遗传调节。我们的建议被发展成三个 凝聚力和连锁目标：目标1：我们将测试早期SDoH的关联性(参见表1，研究计划) 在FFCWS中收集，包括整体CVH状态(14分制)和CVH的7个具体指标中的每一个，位于 年龄约22岁(N=2400)。目标2：我们将评估早期SDoH与存在的关联 用颈动脉超声测定FFCWS(n~1800)亚临床青年CVD的范围。 目标3：我们将：a)检查表观遗传措施(DNA甲基化，dNaM，在9，15， 和22岁)患有上游早期SDoH和下游青壮年CVH和亚临床CVD；b)探索 DNaM对已发现的早期SDoH与青壮年CVH和 亚临床脑血管病，说明已知的遗传效应与脑血管病和亚临床脑血管病的关系。

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.