Gestational diabetes & diabetes in pregnancy
Maternal and fetal genetic predispositions to insulin deficiency and resistance affect fetal growth through distinct pathways
Authors' conclusion
Reduced fetal growth may be driven by lipodystrophy-related insulin resistance and IFG-related insulin deficiency pathways.
Study context
- Population
- Multi-ethnic mother-infant pairs; 2SMR in Europeans
- Participants
- 5,065 mother-infant pairs
- Comparison
- Maternal vs fetal genetic predispositions to insulin deficiency and resistance
- Outcome
- Fetal growth outcomes: birthweight, sum of skinfold thicknesses (SSF), LGA and small-for-gestational-age (SGA) births
Methodological detailsmulti-ethnic, partitioned polygenic risk scores, mediation analysis, co-localisation analyses
- Multi-ethnic
- Partitioned polygenic risk scores
- Mediation analysis
- Co-localisation analyses
Performance
As reported in the abstract
Fetal growth
- Fetal T2D polygenic risk score (PRS) and partitioned polygenic risk scores (pPRSs) for lipodystrophy-related insulin resistance and impaired fasting glucose (IFG)-related insulin deficiency associated with lower birthweight and SSF
- Maternal T2D PRS and pPRSs for IFG-related insulin deficiency and obesity-related insulin resistance associated with higher offspring birthweight, SSF and large-for-gestational-age (LGA)
- Associations consistent across five ethnic groups
Further findings
Mediation of maternal genetic effects
- Maternal post-load hyperglycaemia mediated effect of T2D PRS
- 44.2%
- Maternal post-load hyperglycaemia mediated effect of IFG pPRS
- 34.2%
- Maternal BMI mediated effect of Obesity pPRS
- 43.4%
2SMR in Europeans
- Consistent results; fetal insulin sensitivity index and corrected insulin response associated with higher birthweight
Co-localisation
- Some loci with shared causal variants acted through multiple pathways, incl. CDKAL1, TCF7L2, ADCY5 and MACF1
Original publication
Maternal and fetal genetic predispositions to insulin deficiency and resistance affect fetal growth through distinct pathways. Diabetologia. Published 3 February 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →