As two different diagnostic GDM criteria were applied (IADPSG or the modified 99' WHO) in the two participating countries the following protocol was employed for the analysis of genotype associations: we first had to reclassify the entire dataset of the whole study population according to both criteria based on the OGTT results (FPG and 2 hour PG values) as a ‘diagnosis stratification procedure’. This was possible since there was no medical intervention prior to the 75g OGTT and the test itself was performed in the standardized time-frame of gestation (24th-28th gestational week). Those individuals in whom the GDM diagnosis was established exclusively on the basis of the 60 min OGTT result remained in the GDM group in the ‘diagnosis stratification procedure’. Such cases are rare (less than 5.7% according to the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study [24 (link)] and 13% in the participating Austrian study population). We have performed all binary analysis twice, first using the 99’ modified WHO criteria and second using the IADPSG criteria.
A set of 77 SNPs were selected based on the results of prior genome wide association studies (GWAS) on T2D, BMI, Insulin resistance (IR), Insulin secretion/ beta cell function, plasma glucose or serum insulin level traits. Functionally, the reported genes were suggested to be implicated in the incretin effect, beta-cell function or genesis, potassium channel function, amyloid formation, zinc transport, insulin resistance, obesity development, insulin-like growth factor (IGF) system, vessel formation, glucose homeostasis, circadian rhythm, neuronal regulation of appetite, energy balance or immunoregulation (S1 Table).
Subsequently we provided two numerically different odds ratios and p-values for each gene variants that were significantly associated with GDM according to the corresponding diagnostic system applied in the analysis.
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