Abstract

BACKGROUND AND AIM: Excess weight is a global public health challenge affecting millions of people, including younger age groups. The human exposome concept presents a novel opportunity to comprehensively characterize all non-genetic disease determinants at particularly susceptible time windows. 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 environment-wide association study using the U.S. National Health and Nutrition Examination Survey (NHANES) survey of 2003-2004 for discovery of associations between the study population characteristics and BMI and the 2013-2014 survey to replicate the analysis. We included non-diabetic and non-pregnant adolescents aged 12-18 years-old. 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, education, smoking, and income to poverty ratio. RESULTS:A total of 1899 (18.4% overweight and 18.1% obese) and 1224 (18.5% overweight and 20.6% obese) participants were identified in the target study population of the discovery and replication dataset, respectively. Retained exposure factors included 63 dietary and 50 clinical variables. After correction of false-discovery rate (FDR), univariable regression identified 10 and 13 clinical variables in the discovery and replication dataset, respectively. Multivariable regression identified 4 clinical variables in discovery dataset (uric acid; alanine aminotransferase; gamma glutamyl transferase and triglycerides) of which only uric acid remained significant in the replication dataset after FDR correction. CONCLUSIONS:Associations between BMI and different nutritional and clinical factors were explored and identified in adolescents. Future studies are warranted to investigate the possible role of uric acid as an early-stage biomarker of increased BMI and associated pathologies among adolescents and to replicate these findings to other populations. KEYWORDS: exposome, environment-wide association study, biomarker

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