Abstract MP027: Gene-environment Interaction Analysis Reveals Evidence for Independent Influences of Physical Activity and Sedentary Behavior on Obesity: Results From the Hispanic Community Health Study/study of Latinos (HCHS/SOL)

Abstract

Background: Studies using self-reported data support gene-physical activity interaction on obesity, yet the influence of sedentary behavior, distinct from lack of physical activity, on genetic associations with obesity remains unclear. Methods: We examined interactions of accelerometer-measured physical activity and sedentary behavior with genetic variants on BMI/obesity risk in 9,645 participants aged 18-74 years from the HCHS/SOL, a population-based cohort of US Hispanics/Latinos (2008-2011). A genetic risk score (GRS) was calculated by summing the BMI-increasing alleles of known 97 SNPs (identified primarily in European-ancestry in the GIANT BMI GWAS; P <5х10 -8 ). Specific GRSs were also calculated based on the possible biological categories of these SNPs. Results: The overall GRS was significantly associated with BMI in the HCHS/SOL (β=0.65 per SD [~6-allele increase]; P=1.0х10 -39 ). The genetic effect on BMI was stronger in participants with lower moderate-to-vigorous physical activity (MVPA) (1 st tertile, <8min/day) compared to those with higher MVPA (3 rd tertile, >23min/day) (0.78 [0.10] vs 0.39 [0.10]; P int =0.005), as well as in participants with more sedentary time (3 rd tertile, >13h/day) compared to those with less sedentary time (1 st tertile, <11h/day) (0.73 [0.1] vs 0.44 [0.1]; P int =0.005). The genetic effects on obesity risk were stronger in participants with lower MVPA (P int =0.016) or more sedentary time (P int =0.016). Interactions of GRS with MVPA and sedentary behavior remained significant after further adjustment for each other. Of note, 4 biological category-specific GRSs showed nominally significant interactions with both MVPA and sedentary behavior, while a number of different GRSs interacted with only MVPA or sedentary behavior, in relation to BMI ( Figure ). Conclusions: Our data suggest that both increasing physical activity and reducing sedentary behavior may attenuate the genetic association with obesity, possibly through interacting with shared and different genetic pathways.