基于函数型混合效应模型的纵向队列数据轨迹分析方法研究

本项目拟在心血管疾病生命历程纵向队列设计下，研究适合稀疏和不规则生命历程纵向数据轨迹分析的函数型混合效应模型，通过统计模拟和实际数据分析，比较和探讨混合效应模型、潜在类别混合模型、函数型混合效应模型的增长曲线拟合和轨迹聚类效果，并提出增长速率和曲线下面积等轨迹分析指标，研究生命历程关键\敏感期和累积效应模型。融合“山东省多中心纵向监测健康体检队列”（中国汉族）和“美国Bogalusa心脏研究队列”（黑人和白人）3个种族的生命历程纵向队列数据（4-16次测量，年龄覆盖4-80岁），结局变量为CVD亚临床病变及医保匹配的CVD记录。研究生命历程中心血管代谢性危险因素影响CVD发病的累积效应和关键/敏感期，为CVD病因预防方法和早期干预最佳时机的识别提供科学依据。本项目将为生命历程流行病学纵向数据分析提供新的研究思路和统计方法，对于心血管疾病早期预防和干预具有重要的理论和实际意义。

This project aims to develop appropriate functional mixed effects model for the trajectory analysis of sparse and irregular life-course longitudinal cohort data, under the life-course longitudinal cohort design of cardiovascular disease (CVD). The performances of growth curve fitting and trajectory clustering of three statistical methods (including linear mixed effects model, latent class mixed model, and functional mixed effects model) will be examined and compared by the statistical simulation and real data analysis. In addition, 10 trajectory parameters will be proposed, including year rate of change (slope) and the area under the growth curve (long-term burden), to identify the critical/sensitive periods and cumulative effect in the life-course. This research project includes three ethnical longitudinal cohorts: Chinese Han, American Blacks and Whites (serially examined 4-16 times, age range=4-80 years). Cardiovascular disease (CVD) outcomes include CVD events collected from medical insurance database, metabolic syndrome and subclinical changes, such as left ventricular hypertrophy, carotid intima-media thickness, and pulse wave velocity. The growth curves of cardio-metabolic risk factors will be constructed by using functional mixed effects model for the trajectory analyses, and examine the critical/sensitive periods and cumulative effect of cardio-metabolic risk factors during the CVD development in the life-course (especially childhood and young adulthood). This project will provide new research strategies and novel statistical methodology and R packages of trajectory analysis for CVD life-course epidemiology. This research project has implications in understanding pathophysiological mechanisms and practical significance for developing strategies for the early prevention and intervention of CVD.