Leisure-time physical activity (LTPA) is a well-established modifiable lifestyle determinant for multiple cardio-metabolic outcomes including obesity, type 2 diabetes, and cardiovascular disease. However, current understanding of the genetic architecture that may determine LTPA remains very limited. Therefore, this study aimed to examine the role of genetic factors in affecting LTPA, which has yet to be investigated comprehensively and in-depth.
[Photo: Dr. Xiaochen Lin]
This study, led by Dr. Xiaochen Lin, postdoctoral fellow in the Center for Global Cardiometabolic Health (CGCH) at the Brown University School of Public Health, conducted the first genome-wide assessment in three major national cohort studies of diverse ethnic populations in the United States, the Women’s Health Initiative (n=11,865), the Jackson Heart Study (n=3,015), and the Framingham Heart Study (n=7,339). The authors analyzed these well-characterized big data following a standardized protocol while empolying cutting-edge genome-wide association analysis, sequence kernel association tests, pathway analysis, coupled with functional annotation and expression quantitative trait loci analysis.
Ethnicity-specific genetic signals were investigated respectively for African Americans (AA) and European Americans (EA). Two novel variants, rs116550874 (meta-analysis: P = 1.63 × 10) and rs3792874 (meta-analysis: P = 8.33 × 10), were discovered to be associated with LTPA in AA; rs28524846 (meta-analysis: P = 1.30 × 10) was identified for EA. The team also confirmed four previously reported loci (GABRG3, CYP19A1, PAPSS2 and CASR; P for lead SNPs < 0.005). Further fine-mapping and functional annotation indicated that several identified loci (novel and replicated) are involved in 1) the homeostatic drive coupled with the reward system and 2) the development and regulation of the capacity to perform LTPA.
Senior author, Dr. Simin Liu, professor of epidemiology and medicine and director of CGCH states that findings from the current study clearly demonstrated that genetic predisposition plays a critically important role in determining human physical activity levels which warrant further investigation. “our discoveries generated novel insights into the etiology of many complex diseases related to physical activity and potential new molecular targets for lifestyle interventions.” Dr. Lin stated.
Other investigators included Dr. Rossi Luo, assistant professor of biostatistics, who was a coauthor of this paper.
This article was published in Medicine & Science in Sports & Exercise