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

Objective To determine whether an explained‐variance genetic risk score ( GRS ), with 36 single nucleotide polymorphisms ( SNP s) previously associated with type 2 diabetes ( T 2 D ), is also associated with gestational diabetes mellitus ( GDM ), and with the progression to pre‐diabetes and T 2 D among women with prior GDM . Design A cohort study. Setting Clinical investigation unit of L aval U niversity, Q uebec, C anada. Population A cohort of 214 women with prior GDM and 82 controls recruited between 2009 and 2012. Methods Associations between the GRS and GDM . Main outcomes measures GDM and prevalence of pre‐diabetes and T 2 D . 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 T 2 D 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 T 2 D . 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 T 2 D in women with prior GDM .