Gestational diabetes mellitus (GDM) affects ~14% of pregnancies and is linked to adverse pregnancy outcomes and increased maternal type 2 diabetes mellitus (T2DM) risk. The GenDiP Consortium conducted trans-generational, multi-ancestry genome-wide association study meta-analyses of GDM and pregnancy glycemic traits in up to 38,305 GDM cases and 776,145 controls. We identified 37 GDM-associated loci (19 novel) and five novel loci for glycemic traits, all operating through the maternal genome. Most GDM loci overlapped with T2DM and non‑pregnant glycemic traits, with limited evidence for pregnancy‑specific effects. MTNR1B showed pregnancy‑enhanced effects on 2‑hour glucose, potentially mediated by interaction with GPR61, a novel GDM locus, suggesting a gestation‑specific melatonin-glucose signalling axis. We also observed ancestry‑specific effects at the fasting glucose locus ABCB11, with opposite directions in European and East Asian populations. Our findings provide new insights into the genetic architecture of GDM and highlight the need for larger, ancestrally diverse studies.

The authors have declared no competing interest.

Details of funding received for each contributing cohort are available in the supplementary materials.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

All thirty studies contributing to this work were approved by the relevant institutional ethics review boards. A full list of cohort-specific approvals is provided as supplementary material. All sources of data had been de-identified prior to use in our study

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

GWAS summary statistics are available via the University of Queensland eSpace repository: maternal multi-ancestry GWAS (https://espace.library.uq.edu.au/view/UQ:0aa6ba4), maternal ancestry-specific GWAS (EUR/EAS; https://espace.library.uq.edu.au/view/UQ:2e6c470) and DINGO analyses (https://espace.library.uq.edu.au/view/UQ:ed470a2).