Genome-Wide Genetic Analysis of Dropout in a Controlled Exercise Intervention in Sedentary Adults With Overweight or Obesity and Cardiometabolic Disease
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<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 < .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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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 https://hdl.handle.net/10161/30401.
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Scholars@Duke
Rong Jiang
Katherine Collins
Katherine A. Collins-Bennett, 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.
Ilene C. Siegler
My research efforts are in the area of developmental health psychology and organized around understanding the role of personality in health and disease in middle and later life.
My primary research activity is as Principal Investigator of the UNC Alumni Heart Study (UNCAHS) a prospective epidemiologic study of 5000 middle aged men and women and 1200 of their spouses that evaluates the role of personality on coronary heart disease and coronary heart disease risk, cancer, and normal aging.
As head of Cancer Prevention Research Unit , I study the role of psychological factors related to mammography behavior and estrogen replacement therapy is being studied in UNCAHS women.
REPRESENTATIVE PUBLICATIONS
Siegler, I.C., Zonderman, A.B., Barefoot, J.C., Williams, R.B., Jr., Costa, P.T., Jr., & McCrae, R. R. (1990). Predicting personality from college MMPI scores: Implications for follow-up studies in psychosomatic medicine. Psychosomatic Medicine, 52, 644-652.
Siegler, I.C., Peterson, B.L., Barefoot, J.C., & Williams, R.B. (1992). Hostility during late adolescence predicts coronary risk factors at midlife. American Journal of Epidemiology, 138(2), 146-154.
Siegler, I.C., Peterson, B.L., Barefoot, J.C., Harvin, S.H. Dahlstrom, W.G., Kaplan, B.H., Costa, P.T. Jr., & Williams, R.B. (1992). Using college alumni populations in epidemiologic research: The UNC Alumni Heart Study. Journal of Clinical Epidemiology, 45(11), 1243-1250.
Siegler, I.C., Dawson, D.V., & Welsh, K.A. (1994). Caregiver ratings of personality change in Alzheimer's disease patients: A replication. Psychology and Aging, 9, 464-466.
Siegler, I.C., Feaganes, J.R., & Rimer, B.K. (1995). Predictors of adoption of mammography in women under age 50. Health Psychology, 14, 274-278.
1/13/99
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