Genetic determinants of glucose levels in pregnancy: genetic risk scores analysis and GWAS in the Norwegian STORK cohort

in European Journal of Endocrinology
Correspondence should be addressed to G-H Moen; Email: g.h.o.moen@studmed.uio.no
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Objective

Hyperglycaemia during pregnancy increases the risk of adverse health outcomes in mother and child, but the genetic aetiology is scarcely studied. Our aims were to (1) assess the overlapping genetic aetiology between the pregnant and non-pregnant population and (2) assess the importance of genome-wide polygenic contributions to glucose traits during pregnancy, by exploring whether genetic risk scores (GRSs) for fasting glucose (FG), 2-h glucose (2hG), type 2 diabetes (T2D) and BMI in non-pregnant individuals were associated with glucose measures in pregnant women.

Methods

We genotyped 529 Norwegian pregnant women and constructed GRS from known genome-wide significant variants and SNPs weakly associated (p > 5 × 10−8) with FG, 2hG, BMI and T2D from external genome-wide association studies (GWAS) and examined the association between these scores and glucose measures at gestational weeks 14–16 and 30–32. We also performed GWAS of FG, 2hG and shape information from the glucose curve during an oral glucose tolerance test (OGTT).

Results

GRSFG explained similar variance during pregnancy as in the non-pregnant population (~5%). GRSBMI and GRST2D explained up to 1.3% of the variation in the glucose traits in pregnancy. If we included variants more weakly associated with these traits, GRS2hG and GRST2D explained up to 2.4% of the variation in the glucose traits in pregnancy, highlighting the importance of polygenic contributions.

Conclusions

Our results suggest overlap in the genetic aetiology of FG in pregnant and non-pregnant individuals. This was less apparent with 2hG, suggesting potential differences in postprandial glucose metabolism inside and outside of pregnancy.

Downloadable materials

  • Supplementary Information
  • Supplementary Figure 1
  • Supplementary Figure 2
  • Supplementary Figure 3
  • Supplementary Figure 4
  • Supplementary Figure 5
  • Supplementary Figure 6
  • Supplementary Figure 7
  • Supplementary Figure 8
  • Supplementary Figure 9
  • Supplementary Figure 10
  • ST1: Overview of SNPs in GRSFG of known variants from the MAGIC consortium
  • ST2: Overview of SNPs in GRS2hG of known variants from the MAGIC consortium
  • ST3: Overview of SNPs in GRST2D of known variants from the DIAGRAM consortium
  • ST4: Overview of SNPs in GRSBMI of known variants from the GIANT consortium
  • ST5: Significant SNPs from the GWAS

 

     European Society of Endocrinology

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    Flowchart for women included in the study. 485 women had 5 OGTT measurements at both GW 14–16 and 30–32. GW, gestational week; OGTT, oral glucose tolerance test.

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