Analysis of Multiple Biomarkers Using Structural Equation Modeling

Tob Regul Sci. 2020 Jul;6(4):266-278. doi: 10.18001/trs.6.4.4.

Abstract

Objectives: When examining the relationship between smoking intensity and toxicant exposure biomarkers in an effort to understand the potential risk for smoking-related disease, individual biomarkers may not be strongly associated with smoking intensity because of the inherent variability in biomarkers. Structural equation modeling (SEM) offers a powerful solution by modeling the relationship between smoking intensity and multiple biomarkers through a latent variable.

Methods: Baseline data from a randomized trial (N = 1250) were used to estimate the relationship between smoking intensity and a latent toxicant exposure variable summarizing five volatile organic compound biomarkers. Two variables of smoking intensity were analyzed: the self-report cigarettes smoked per day and total nicotine equivalents in urine. SEM was compared with linear regression with each biomarker analyzed individually or with the sum score of the five biomarkers.

Results: SEM models showed strong relationships between smoking intensity and the latent toxicant exposure variable, and the relationship was stronger than its counterparts in linear regression with each biomarker analyzed separately or with the sum score.

Conclusions: SEM is a powerful multivariate statistical method for studying multiple biomarkers assessing the same class of harmful constituents. This method could be used to evaluate exposure from different combusted tobacco products.

Keywords: biological marker (biomarker); cigarette smoke; latent variable; multivariate statistical method; structural equation modelling.