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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Gunn Helen Moen
  • Marissa LeBlanc
  • Christine Sommer
  • Rashmi B. Prasad
  • Tove Lekva
  • Kjersti R. Normann
  • Elisabeth Qvigstad
  • Leif Groop
  • Kåre I. Birkeland
  • David M. Evans
  • Kathrine F. Frøslie
Organisations
External organisations
  • Oslo university hospital
  • University of Oslo
  • Institute for Molecular Medicine Finland (FIMM)
  • University of Helsinki
  • University of Queensland
  • University of Bristol
  • Norwegian National Advisory Unit on Women's Health
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Medical Genetics
Original languageEnglish
Pages (from-to)363-372
Number of pages10
JournalEuropean journal of endocrinology
Volume179
Issue number6
Publication statusPublished - 2018
Publication categoryResearch
Peer-reviewedYes