@article {1125406, title = {Genetic Susceptibility, Change in Physical Activity, and Long-term Weight Gain}, journal = {Diabetes}, volume = {66}, number = {10}, year = {2017}, month = {2017 Oct}, pages = {2704-2712}, abstract = {Whether change in physical activity over time modifies the genetic susceptibility to long-term weight gain is unknown. We calculated a BMI-genetic risk score (GRS) based on 77 BMI-associated single nucleotide polymorphisms (SNPs) and a body fat percentage (BF\%)-GRS based on 12 BF\%-associated SNPs in 9,390 women from the Nurses{\textquoteright} Health Study (NHS) and 5,291 men from the Health Professionals Follow-Up Study (HPFS). We analyzed the interactions between each GRS and change in physical activity on BMI/body weight change within five 4-year intervals from 1986 to 2006 using multivariable generalized linear models with repeated-measures analyses. Both the BMI-GRS and the BF\%-GRS were associated with long-term increases in BMI/weight, and change in physical activity consistently interacted with the BF\%-GRS on BMI change in the NHS (P for interaction = 0.025) and HPFS (P for interaction = 0.001). In the combined cohorts, 4-year BMI change per 10-risk allele increment was -0.02 kg/m(2) among participants with greatest increase in physical activity and 0.24 kg/m(2) among those with greatest decrease in physical activity (P for interaction \< 0.001), corresponding to 0.01 kg versus 0.63 kg weight changes every 4 years (P for interaction = 0.001). Similar but marginal interactions were observed for the BMI-GRS (P for interaction = 0.045). Our data indicate that the genetic susceptibility to weight gain may be diminished by increasing physical activity.}, keywords = {Adult, Aged, Body Mass Index, Body Weight, Exercise, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Prospective Studies, Weight Gain}, issn = {1939-327X}, doi = {10.2337/db17-0071}, author = {Wang, Tiange and Huang, Tao and Heianza, Yoriko and Sun, Dianjianyi and Zheng, Yan and Ma, Wenjie and Jensen, Majken K and Kang, Jae H and Wiggs, Janey L and Pasquale, Louis R and Rimm, Eric B and Manson, JoAnn E and Hu, Frank B and Willett, Walter C and Qi, Lu} }