title: Multiple metabolic genetic risk scores and type 2 diabetes risk in three racial/ethnic groups.
abstract: CONTEXT/RATIONALE: Meta-analyses of genome-wide association studies have identified many single-nucleotide polymorphisms associated with various metabolic and cardiovascular traits, offering us the opportunity to learn about and capitalize on the links between cardiometabolic traits and type 2 diabetes (T2D).
  
  
  METHODS
  In multiple datasets comprising over 30 000 individuals and 3 ethnic/racial groups, we calculated 17 genetic risk scores (GRSs) for glycemic, anthropometric, lipid, hemodynamic, and other traits, based on the results of recent trait-specific meta-analyses of genome-wide association studies, and examined associations with T2D risk. Using a training-testing procedure, we evaluated whether additional GRSs could contribute to risk prediction.
  
  
  RESULTS
  In European Americans, we find that GRSs for T2D, fasting glucose, fasting insulin, and body mass index are associated with T2D risk. In African Americans, GRSs for T2D, fasting insulin, and waist-to-hip ratio are associated with T2D. In Hispanic Americans, GRSs for T2D and body mass index are associated with T2D. We observed a trend among European Americans suggesting that genetic risk for hyperlipidemia is inversely associated with T2D risk. The use of additional GRSs resulted in only small changes in prediction accuracy in multiple independent validation datasets.
  
  
  CONCLUSIONS
  The analysis of multiple GRSs can shed light on T2D etiology and how it varies across ethnic/racial groups. Our findings using multiple GRSs are consistent with what is known about the differences in T2D pathogenesis across racial/ethnic groups. However, further work is needed to understand the putative inverse correlation of genetic risk for hyperlipidemia and T2D risk and to develop ethnic-specific GRSs.
authors.affiliation: Mel and Enid Zuckerman College of Public Health (Y.C.K.), Division of Epidemiology and Biostatistics, University of Arizona, Tucson, Arizona 85724; Scripps Translational Science Institute (N.E.W.), La Jolla, California 92037; and Section on Statistical Genetics (A.I.V., G.d.l.C.), Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Wineinger
authors.forename: Ana I
authors.initials: AI
authors.lastname: Vazquez
authors.forename: Gustavo
authors.initials: G
authors.lastname: de Los Campos
mesh_terms: D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics* / Q000706:statistics & numerical data*; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006801:Humans; D012307:Risk Factors; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data