Gestational diabetes & diabetes in pregnancy
Genetics of glucose homeostasis in pregnancy and postpartum
Authors' conclusion
Our findings support the hypothesis that there are both overlaps and differences between the genetic architecture of glycaemia-related traits during and outside of pregnancy. Genetic variants at several loci, including PCSK1, PPP1R3B, MTNR1B and IGF1, appear to influence glycaemic regulation in a unique fashion during pregnancy. Future studies in larger cohorts will be needed to replicate the present findings, fully characterise the genetics of maternal glycaemia during pregnancy and determine similarities to and differences from the non-gravid state.
Study context
- Population
- Pregnant participants in the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) Study, with follow-up at 11–14 years postpartum
- Participants
- 8,067 vs 3,977
- Comparison
- Genetic associations of glycaemia-related traits during pregnancy vs 11-14 years postpartum
- Pregnancyn = 8,067
- Postpartumn = 3,977reference
- Outcome
- Loci associated with glycaemia-related traits during pregnancy
- Follow-up
- ≈28 weeks' gestation
Methodological detailsBayesian classification algorithm
- Bayesian classification algorithm
Main finding
As reported in the abstract
- Fasting glucose: SNPs in six loci (GCKR, G6PC2, GCK, PPP1R3B, PCSK1 and MTNR1B)
- 1 h glucose: CDKAL1 and MTNR1B; 2 h glucose: MTNR1B and HKDC1
- Insulin secretion: CDKAL1 and MTNR1B
- Fasting C-peptide: multiple loci incl. GCKR, IQSEC1, PPP1R3B, IGF1 and BACE2
- 1 h C-peptide: GCKR and BACE2; insulin sensitivity: GCKR, IQSEC1 and BACE2
- Not previously reported in non-pregnancy cohorts: MTNR1B with 2 h glucose, BACE2 with fasting and 1 h C-peptide and insulin sensitivity, IQSEC1 with fasting C-peptide and insulin sensitivity
Further findings
Pregnancy-predominant effect (Bayesian classification): lead SNP effect greater during pregnancy vs 11-14 years postpartum
- Fasting glucose: PCSK1 and PPP1R3B
- 2 h glucose: three loci, including MTNR1B
- Fasting C-peptide: six loci, including IGF1
Original publication
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