An approach to assess and adjust for the influence of multicollinear covariates on metabolomics association patterns-applied to a study of the associations between a comprehensive lipoprotein profile and the homeostatic model assessment of insulin resistance.

Olav M Kvalheim, Tarja Rajalahti, Eivind Aadland
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Abstract

Introduction: Comprehensive lipoprotein profiling using proton nuclear magnetic resonance (NMR) spectroscopy of serum represents an alternative to the homeostatic model assessment of insulin resistance (HOMA-IR). Both adiposity and physical (in)activity associate to insulin resistance, but quantification of the influence of these two lifestyle related factors on the association pattern of HOMA-IR to lipoproteins suffers from lack of appropriate methods to handle multicollinear covariates.

Objectives: We aimed at (i) developing an approach for assessment and adjustment of the influence of multicollinear and even linear dependent covariates on regression models, and (ii) to use this approach to examine the influence of adiposity and physical activity on the association pattern between HOMA-IR and the lipoprotein profile.

Methods: For 841 children, lipoprotein profiles were obtained from serum proton NMR and physical activity (PA) intensity profiles from accelerometry. Adiposity was measured as body mass index, the ratio of waist circumference to height, and skinfold thickness. Target projections were used to assess and isolate the influence of adiposity and PA on the association pattern of HOMA-IR to the lipoproteins.

Results: Adiposity explained just over 50% of the association pattern of HOMA-IR to the lipoproteins with strongest influence on high-density lipoprotein features. The influence of PA was mainly attributed to a strong inverse association between adiposity and moderate and high-intensity physical activity.

Conclusion: The presented covariate projection approach to obtain net association patterns, made it possible to quantify and interpret the influence of adiposity and physical (in)activity on the association pattern of HOMA-IR to the lipoprotein features.

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一种评估和调整多重共线性协变量对代谢组学关联模式影响的方法-应用于综合脂蛋白谱与胰岛素抵抗的稳态模型评估之间的关联研究。
使用血清质子核磁共振(NMR)光谱的综合脂蛋白谱分析代表了胰岛素抵抗(HOMA-IR)稳态模型评估的另一种选择。肥胖和身体活动都与胰岛素抵抗有关,但量化这两个生活方式相关因素对HOMA-IR与脂蛋白的关联模式的影响,缺乏适当的方法来处理多重共线性协变量。目的:我们的目标是(i)开发一种方法来评估和调整多元共线性甚至线性相关协变量对回归模型的影响,以及(ii)使用这种方法来检查肥胖和身体活动对HOMA-IR和脂蛋白谱之间的关联模式的影响。方法:对841名儿童进行血清质子核磁共振(NMR)脂蛋白谱和加速度计体力活动(PA)强度谱分析。肥胖的测量方法包括身体质量指数、腰围与身高之比和皮褶厚度。目标预测用于评估和分离肥胖和PA对HOMA-IR与脂蛋白的关联模式的影响。结果:肥胖解释了超过50%的HOMA-IR与对高密度脂蛋白特征影响最大的脂蛋白的关联模式。PA的影响主要归因于肥胖与中高强度体力活动之间的强烈负相关。结论:所提出的协变量投影方法获得净关联模式,使量化和解释肥胖和身体活动对HOMA-IR与脂蛋白特征的关联模式的影响成为可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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