An Exposome-Wide Association Study On Body Mass Index In Adolescents Using The National Health And Nutrition Examination Survey (NHANES) 2003-2004 And 2013-2014 Data

Background: Excess weight is a public health challenge affecting millions worldwide, including younger age groups. The human exposome concept presents a novel opportunity to comprehensively characterize all non-genetic disease determinants at susceptible time windows. Objective: Our study aimed to describe the association between multiple lifestyle and nutritional exposures and body mass index (BMI) in adolescents using the exposome framework. Methods: We conducted an exposome-wide association study using the U.S. National Health and Nutrition Examination Survey (NHANES) 2003-2004 survey for discovery of associations between the study population characteristics and BMI, and the 2013-2014 survey to replicate analysis. We included non-diabetic and non-pregnant adolescents aged 12-18 years. We analyzed variables available in both survey rounds, with <20% of missing values in relation to BMI z-scores. We performed univariable and multivariable linear regression analysis adjusted for age, sex, race/ethnicity, household smoking, and income to poverty ratio, and corrected for false-discovery rate (FDR). Results: A total of 1899 and 1224 participants were eligible from the 2003-2004 and 2013-2014 survey waves. The weighted proportions of overweight were 18.4% and 18.5% whereas those for obese were 18.1% and 20.6% in 2003-2004 and 2013-2014, respectively. Retained exposure agents included 63 dietary, 57 clinical and 1 physical activity variables. After FDR correction, univariable regression identified 35 and 18 predictors in the discovery and replication datasets, respectively, while multivariable regression identified 20 and 9 predictors in the discovery and replication datasets, respectively. Seven were significant in both datasets: alanine aminotransferase, gamma glutamyl transferase, mean cell volume, segmented neutrophils number, triglycerides; uric acid and white blood cell count. Discussion: This is the first ExWAS study in NHANES describing associations between zBMI, nutritional and clinical factors in adolescents. Future studies are warranted to investigate the role of the identified predictors as early-stage biomarkers of increased BMI and associated pathologies among adolescents and to replicate findings to other populations.