Alcohol consumption has been shown to influence cardiovascular mechanisms in humans, leading to observable alterations in the plasma metabolomic profile. Regression models are commonly employed to investigate these effects, treating metabolomics features as the outcomes and alcohol intake as the exposure. Given the latent dependence structure among the numerous metabolomic features (e.g., co-expression networks with interconnected modules), modeling this structure is crucial for accurately identifying metabolomic features associated with alcohol intake. However, integrating dependence structures into regression models remains difficult in both estimation and inference procedures due to their large or high dimensionality. To bridge this gap, we propose an innovative multivariate regression model that accounts for correlations among outcome features by incorporating an interconnected community structure. Furthermore, we derive closed-form and likelihood-based estimators, accompanied by explicit exact and explicit asymptotic covariance matrix estimators, respectively. Simulation analysis demonstrates that our approach provides accurate estimation of both dependence and regression coefficients, and enhances sensitivity while maintaining a well-controlled discovery rate, as evidenced through benchmarking against existing regression models. Finally, we apply our approach to assess the impact of alcohol intake on $249$ metabolomic biomarkers measured using nuclear magnetic resonance spectroscopy. The results indicate that alcohol intake can elevate high-density lipoprotein levels by enhancing the transport rate of Apolipoproteins A1.

翻译：已有研究表明，饮酒会影响人类的心血管机制，导致血浆代谢组学特征发生可观察到的变化。通常采用回归模型研究这些影响，将代谢组学特征作为结果变量，酒精摄入作为暴露变量。鉴于众多代谢组学特征之间存在潜在依赖结构（例如具有互连模块的共表达网络），准确建模该结构对于识别与酒精摄入相关的代谢组学特征至关重要。然而，由于结果特征数量大或维度高，将依赖结构整合到回归模型中在估计和推断过程中仍存在困难。为弥补这一不足，我们提出一种创新性多元回归模型，通过纳入互连的社区结构来考虑结果特征间的相关性。此外，我们推导出闭式及基于似然的估计量，并分别给出显式精确和显式渐近协方差矩阵估计量。模拟分析表明，与现有回归模型相比，我们的方法能精确估计依赖系数和回归系数，并在严格控制发现率的同时提高敏感性。最后，我们将该方法应用于评估酒精摄入对用核磁共振波谱法测定的249个代谢组学生物标志物的影响。结果表明，饮酒可通过增强载脂蛋白A1的转运速率提高高密度脂蛋白水平。