title: Association of physical activity with lower type 2 diabetes incidence is weaker among individuals at high genetic risk.
abstract: OBJECTIVE
  We examined whether or not the association of physical activity with type 2 diabetes incidence differs according to several types of genetic susceptibility.
  
  
  METHODS
  In a large prospective cohort with 821 incident cases of type 2 diabetes, we examined interactions of physical activity with: (1) each of 65 type 2 diabetes-associated single nucleotide polymorphisms (SNPs); (2) a genetic risk score (GRS) comprising all 65 SNPs; (3) two GRSs comprised of SNPs implicated in insulin resistance (IR) and insulin secretion; (4) GRSs for fasting insulin (FI) and fasting glucose.
  
  
  RESULTS
  We found a significant interaction of physical activity and the type 2 diabetes GRS (p interaction = 0.016), suggesting a weaker protective effect of physical activity in those at high genetic risk. Based on the interactions observed with the IR GRS (p interaction = 0.046) and the FI GRS (p interaction = 0.042), it appears that the overall type 2 diabetes GRS interaction most likely occurs through genetic susceptibility to IR as opposed to insulin secretion. Furthermore, this interaction was more pronounced in women (p interaction = 0.0025) than in men (p interaction = 0.46). No single SNP stood out as displaying a strong interaction with physical activity.
  
  
  CONCLUSIONS
  We conclude that although physical activity appears to have an overall protective effect on type 2 diabetes, this putative effect is weakest among individuals with high genetic risk for type 2 diabetes and IR.
authors.affiliation: Mel and Enid Zuckerman College of Public Health, Division of Epidemiology and Biostatistics, University of Arizona, 1295 N. Martin, Tucson, AZ, 85724, USA, yann@email.arizona.edu.
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Amit
authors.initials: A
authors.lastname: Arora
authors.forename: Chiu-Hsieh
authors.initials: CH
authors.lastname: Hsu
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D004032:Diet; D015444:Exercise / Q000502:physiology*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide