Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease


<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Despite the benefits of exercise, many individuals are unable or unwilling to adopt an exercise intervention.</jats:p> </jats:sec> <jats:sec> <jats:title>Purpose</jats:title> <jats:p>The purpose of this analysis was to identify putative genetic variants associated with dropout from exercise training interventions among individuals in the STRRIDE trials.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We used a genome-wide association study approach to identify genetic variants in 603 participants initiating a supervised exercise intervention. Exercise intervention dropout occurred when a subject withdrew from further participation in the study or was otherwise lost to follow-up.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Exercise intervention dropout was associated with a cluster of single-nucleotide polymorphisms with the top candidate being rs722069 (T/C, risk allele = C) (unadjusted p = 2.2 × 10−7, odds ratio = 2.23) contained within a linkage disequilibrium block on chromosome 16. In Genotype-Tissue Expression, rs722069 is an expression quantitative trait locus of the EARS2, COG7, and DCTN5 genes in skeletal muscle tissue. In subsets of the STRRIDE genetic cohort with available muscle gene expression (n = 37) and metabolic data (n = 82), at baseline the C allele was associated with lesser muscle expression of EARS2 (p &lt; .002) and COG7 (p = .074) as well as lesser muscle concentrations of C2- and C3-acylcarnitines (p = .026).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our observations imply that exercise intervention dropout is genetically moderated through alterations in gene expression and metabolic pathways in skeletal muscle. Individual genetic traits may allow the development of a biomarker-based approach for identifying individuals who may benefit from more intensive counseling and other interventions to optimize exercise intervention adoption.</jats:p> </jats:sec> <jats:sec> <jats:title>Clinical Trial information</jats:title> <jats:p>STRRIDE I = NCT00200993; STRRIDE AT/RT = NCT00275145; STRRIDE-PD = NCT00962962.</jats:p> </jats:sec>






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Publication Info

Jiang, Rong, Katherine A Collins, Kim M Huffman, Elizabeth R Hauser, Monica J Hubal, Johanna L Johnson, Redford B Williams, Ilene C Siegler, et al. (n.d.). Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease. Annals of Behavioral Medicine. 10.1093/abm/kaae011 Retrieved from

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Rong Jiang

Assistant Professor in Head and Neck Surgery & Communication Sciences

Katherine Collins

Medical Instructor in Population Health Sciences

Katherine A. Collins, PhD, NBC-HWC, is a Medical Instructor in the Department of Population Health Sciences and affiliated with the Duke Molecular Physiology Institute at Duke University School of Medicine, and is a board-certified health and wellness coach. She studies barriers and predictors of health-promoting behavior change. The ultimate goal of her translational research is to design trials to optimize health-promoting behaviors for those at risk for "relapse" or ceased behavioral modification, in order to improve long-term health and well-being.


Kim Marie Huffman

Associate Professor of Medicine

Determining the role of physical activity in modulating health outcomes (cardiovascular disease risk) in persons with rheumatologic diseases (rheumatoid arthritis, gout, osteoarthritis)

Integrating clinical rheumatology, basic immunology, metabolism, and exercise science in order to reduce morbidity in individuals with arthritis

Evaluating relationships between circulating and intra-muscular metabolic intermediates and insulin resistance in sedentary as well as individuals engaging in regular exercise

Addressing the role of physical activity in modulating inflammation, metabolism, and functional health in aging populations

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