Am J Epidemiol. 2021 Aug 1;190(8):1533-1540. doi: 10.1093/aje/kwab049.
We examined the way body-weight patterns through the first 4 decades of life relate to gene expression signatures of common forms of morbidity, including cardiovascular disease (CVD), type 2 diabetes (T2D), and inflammation. As part of wave V of the nationally representative National Longitudinal Study of Adolescent to Adult Health (1997-2018) in the United States, mRNA abundance data were collected from peripheral blood (n = 1,132). We used a Bayesian modeling strategy to examine the relative associations between body size at 5 life stages-birth, adolescence, early adulthood, young adulthood, and adulthood-and gene expression-based disease signatures. We compared life-course models that consider critical or sensitive periods, as well as accumulation over the entire period. Our results are consistent with a sensitive-period model when examining CVD and T2D gene expression signatures: Birth weight has a prominent role for the CVD and T2D signatures (explaining 33.1% and 22.1%, respectively, of the total association accounted for by body size), while the most recent adult obesity status (ages 33-39) is important for both of these gene expression signatures (24.3% and 35.1%, respectively). Body size in all life stages was associated with inflammation, consistent with the accumulation model.
我们研究了人生前 40 年的体重模式与心血管疾病（CVD）、2 型糖尿病（T2D）和炎症等常见疾病的基因表达特征之间的关系。作为美国全国青少年至成人健康纵向研究（1997-2018 年）第五波的一部分，我们从外周血中收集了 mRNA 丰度数据（n=1132）。我们使用贝叶斯建模策略来研究 5 个生命阶段（出生、青春期、成年早期、成年早期和成年期）的体型与基于基因表达的疾病特征之间的相对关联。我们比较了考虑关键或敏感时期以及整个时期积累的生命历程模型。当我们检查 CVD 和 T2D 基因表达特征时，我们的结果与敏感时期模型一致：出生体重对 CVD 和 T2D 特征具有重要作用（分别解释了体型总关联的 33.1%和 22.1%），而最近的成年肥胖状况（33-39 岁）对这两个基因表达特征都很重要（分别为 24.3%和 35.1%）。所有生命阶段的体型都与炎症有关，这与累积模型一致。
