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

Moen, Gunn Helen; LeBlanc, Marissa; Sommer, Christine; Prasad, Rashmi B. LU ; Lekva, Tove; Normann, Kjersti R.; Qvigstad, Elisabeth; Groop, Leif LU ; Birkeland, Kåre I. and Evans, David M., et al. (2018) In European journal of endocrinology 179(6). p.363-372
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... (More)

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.

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published
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European journal of endocrinology
volume
179
issue
6
pages
10 pages
publisher
Society of the European Journal of Endocrinology
external identifiers
  • scopus:85056088532
ISSN
0804-4643
DOI
10.1530/EJE-18-0478
language
English
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yes
id
f736fefa-bed3-4b9e-ba1f-3f6543bb0fbc
date added to LUP
2018-11-21 13:04:35
date last changed
2019-02-20 11:36:56
@article{f736fefa-bed3-4b9e-ba1f-3f6543bb0fbc,
  abstract     = {<p>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&gt;5×10−<sup>8</sup>) 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: GRS<sub>FG</sub> explained similar variance during pregnancy as in the non-pregnant population (~5%). GRS<sub>BMI</sub> and GRS<sub>T2D</sub> explained up to 1.3% of the variation in the glucose traits in pregnancy. If we included variants more weakly associated with these traits, GRS<sub>2hG</sub> and GRS<sub>T2D</sub> 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.</p>},
  author       = {Moen, Gunn Helen and LeBlanc, Marissa and Sommer, Christine and Prasad, Rashmi B. and Lekva, Tove and Normann, Kjersti R. and Qvigstad, Elisabeth and Groop, Leif and Birkeland, Kåre I. and Evans, David M. and Frøslie, Kathrine F.},
  issn         = {0804-4643},
  language     = {eng},
  number       = {6},
  pages        = {363--372},
  publisher    = {Society of the European Journal of Endocrinology},
  series       = {European journal of endocrinology},
  title        = {Genetic determinants of glucose levels in pregnancy : Genetic risk scores analysis and GWAS in the Norwegian STORK cohort},
  url          = {http://dx.doi.org/10.1530/EJE-18-0478},
  volume       = {179},
  year         = {2018},
}