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Genetic and environmental (physical fitness and sedentary activity) interaction effects on cardiometabolic risk factors in Mexican American children and adolescents
Authors:Rector Arya  Vidya S. Farook  Sharon P. Fowler  Sobha Puppala  Geetha Chittoor  Roy G. Resendez  Srinivas Mummidi  Jairam Vanamala  Laura Almasy  Joanne E. Curran  Anthony G. Comuzzie  Donna M. Lehman  Christopher P. Jenkinson  Jane L. Lynch  Ralph A. DeFronzo  John Blangero  Daniel E. Hale  Ravindranath Duggirala  Vincent P. Diego
Affiliation:1. Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg, Texas, United States of America;2. South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, Texas, United States of America;3. Department of Medicine, Division of Nephrology, University of Texas Health Science Center, San Antonio, Texas, United States of America;4. Department of Internal Medicine, Section on Molecular Medicine Wake Forest Baptist Health Medical University, Winston‐Salem, NC, United States of America;5. Biomedical and Translational Informatics Institute, Geisinger, Weis Center for Research, Danville, PA, United States of America;6. Department of Food Science, Penn State University, University Park, PA, United States of America;7. Department of Biomedical and Health Informatics, University of Pennsylvania, Philadelphia, PA, United States of America;8. The Obesity Society, Maryland, United States of America;9. Department of Cellular & Structural Biology, University of Texas Health Science Center, San Antonio, Texas, United States of America;10. Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas, United States of America;11. Department of Medicine, Division of Diabetes, University of Texas Health Science Center, San Antonio, Texas, United States of America;12. Penn State Hershey Pediatric Endocrinology, Penn State University, Hershey, PA, United States of America
Abstract:Knowledge on genetic and environmental (G × E) interaction effects on cardiometabolic risk factors (CMRFs) in children is limited.  The purpose of this study was to examine the impact of G × E interaction effects on CMRFs in Mexican American (MA) children (n = 617, ages 6–17 years). The environments examined were sedentary activity (SA), assessed by recalls from “yesterday” (SAy) and “usually” (SAu) and physical fitness (PF) assessed by Harvard PF scores (HPFS). CMRF data included body mass index (BMI), waist circumference (WC), fat mass (FM), fasting insulin (FI), homeostasis model of assessment—insulin resistance (HOMA‐IR), high‐density lipoprotein cholesterol (HDL‐C), triglycerides (TG), systolic (SBP) and diastolic (DBP) blood pressure, and number of metabolic syndrome components (MSC). We examined potential G × E interaction in the phenotypic expression of CMRFs using variance component models and likelihood‐based statistical inference. Significant G × SA interactions were identified for six CMRFs: BMI, WC, FI, HOMA‐IR, MSC, and HDL, and significant G × HPFS interactions were observed for four CMRFs: BMI, WC, FM, and HOMA‐IR. However, after correcting for multiple hypothesis testing, only WC × SAy, FM × SAy, and FI × SAu interactions became marginally significant. After correcting for multiple testing, most of CMRFs exhibited significant G × E interactions (Reduced G × E model vs. Constrained model). These findings provide evidence that genetic factors interact with SA and PF to influence variation in CMRFs, and underscore the need for better understanding of these relationships to develop strategies and interventions to effectively reduce or prevent cardiometabolic risk in children.
Keywords:childhood obesity  G ×   E interaction  genetic correlation  genetic variance  lifestyle modification  physical inactivity  sedentary behavior
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