title: An explained variance-based genetic risk score associated with gestational diabetes antecedent and with progression to pre-diabetes and type 2 diabetes: a cohort study.
abstract: OBJECTIVE
  To determine whether an explained-variance genetic risk score (GRS), with 36 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes (T2D), is also associated with gestational diabetes mellitus (GDM), and with the progression to pre-diabetes and T2D among women with prior GDM.
  
  
  METHODS
  A cohort study.
  
  
  METHODS
  Clinical investigation unit of Laval University, Quebec, Canada.
  
  
  METHODS
  A cohort of 214 women with prior GDM and 82 controls recruited between 2009 and 2012.
  
  
  METHODS
  Associations between the GRS and GDM.
  
  
  METHODS
  GDM and prevalence of pre-diabetes and T2D.
  
  
  RESULTS
  Women with prior GDM had a higher GRS compared with controls (38.6 ± 3.9, 95% CI 38.1-39.1, versus 37.4 ± 3.2, 95% CI 36.7-38.1; P < 0.0001). In women with prior GDM, the explained-variance GRS was higher for pre-diabetic women compared with women who remained normoglucotolerant at testing (1.21 ± 0.18, 95% CI 1.18-1.23, versus 1.17 ± 0.15, 95% CI 1.13-1.20; P < 0.0001). Similarly, women with T2D had a higher explained-variance GRS compared with women with prior GDM who remained normoglucotolerant (1.20 ± 0.18, 95% CI 1.14-1.25, versus 1.17 ± 0.17, 95% CI 1.13-1.20; P < 0.0001). The predictive effects of the explained-variance GRS, age, and body mass index (BMI), or the additive effects of the three variables, were tested for pre-diabetes and T2D. We observed an area under the curve of 0.6269 (95% CI 0.5638-0.6901) for age and BMI, and adding the explained-variance GRS into the model increased the area to 0.6672 (95% CI 0.6064-0.7281) for the prediction of pre-diabetes.
  
  
  CONCLUSIONS
  An explained-variance GRS is associated with both GDM and progression to pre-diabetes and T2D in women with prior GDM.
authors.affiliation: Department of Food Sciences and Nutrition, Laval University, Quebec City, QC, Canada; Institute of Nutrition and Functional Foods (INAF), Laval University, Quebec City, QC, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Cormier
authors.forename: J
authors.initials: J
authors.lastname: Vigneault
authors.forename: V
authors.initials: V
authors.lastname: Garneau
authors.forename: A
authors.initials: A
authors.lastname: Tchernof
authors.forename: M-C
authors.initials: MC
authors.lastname: Vohl
authors.forename: S J
authors.initials: SJ
authors.lastname: Weisnagel
authors.forename: J
authors.initials: J
authors.lastname: Robitaille
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D002170:Canada / Q000453:epidemiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D016640:Diabetes, Gestational / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D015995:Prevalence; D012307:Risk Factors
keywords: Genetic risk score; gestational diabetes mellitus; susceptibility genes; type 2 diabetes