Distinct and shared genetic architectures of Gestational diabetes mellitus and Type 2 Diabetes Mellitus.
A ElliottR K WaltersMatti PirinenM KurkiN JunnaJ GoldsteinM P ReeveH SiirtolaS LemmeläP Turleynull nullA PalotieM DalyElisabeth WidenPublished in: medRxiv : the preprint server for health sciences (2023)
Gestational diabetes mellitus (GDM) affects more than 16 million pregnancies annually worldwide and is related to an increased lifetime risk of Type 2 diabetes (T2D). The diseases are hypothesized to share a genetic predisposition, but there are few GWAS studies of GDM and none of them is sufficiently powered to assess whether any variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen Study and identified 13 GDM-associated loci including 8 novel loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into two distinct categories - one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis, and placental expression. These results pave the way for an improved biological understanding of GDM pathophysiology and its role in the development and course of T2D.
Keyphrases
- genome wide association study
- genome wide
- copy number
- pregnancy outcomes
- pregnant women
- type diabetes
- poor prognosis
- preterm birth
- induced apoptosis
- cardiovascular disease
- signaling pathway
- blood pressure
- binding protein
- gene expression
- skeletal muscle
- oxidative stress
- long non coding rna
- insulin resistance
- gestational age
- resting state
- drug induced