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<p>Gestational diabetes mellitus (GDM) affects ~14% of pregnancies and increases maternal type 2 diabetes mellitus (T2DM) risk. The GenDiP Consortium presents 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 identify 37 GDM-associated loci (7 novel) and five novel loci for pregnancy glycemic traits, all operating through the maternal genome. We classify 12 GDM variants with stronger effects in GDM than T2DM into five biologically informed categories, revealing pleiotropy patterns, pregnancy-dependent effect modification, and diagnostic heterogeneity. While all these loci overlap with T2DM and/or non-pregnant glycaemic traits, four (<i>G6PC2, CAST-PCSK1, HKDC1, FOXA2</i>) lack genome-wide-significant T2DM associations; <i>GCK</i> shows distinct causal variants for GDM, and <i>MTNR1B</i> exhibits pregnancy-amplified effects. Our findings provide new genetic insights into GDM and highlight the need for larger, ancestrally diverse studies of GDM and glycaemic traits during pregnancy to understand potential pregnancy-specific effects.</p>

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Multi-ancestry, trans-generational GWAS meta-analysis of gestational diabetes and glycaemic traits during pregnancy reveals limited evidence of pregnancy-specific genetic effects

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月1日

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  • Caroline Brito Nunes,
  • Valentina Rukins,
  • Aminata H. Cisse,
  • Frédérique White,
  • Nancy McBride,
  • Alan Kuang,
  • Catherine Allard,
  • Justiina Ronkainen,
  • Alice Hughes,
  • Amanda Elliott,
  • Gudmar Thorleifsson,
  • Marc Vaudel,
  • Triin Laisk,
  • Yuqin Gu,
  • Amel Lamri,
  • Li Chen,
  • Johanna Tuhkanen,
  • Jari Lahti,
  • Lucinda Calas,
  • Manon Muntaner,
  • Ville Karhunen,
  • Jaewon Choi,
  • Anni Heiskala,
  • Gad Hatem,
  • Nicolas Fragoso-Bargas,
  • Sheryl L. Rifas-Shiman,
  • Guillermo Paz-Lopez,
  • Sara E. Stinson,
  • Bishwajit Bhowmik,
  • Emma Ahlqvist,
  • Jean-Francois Deleuze,
  • Johan G. Eriksson,
  • Jongseok Park,
  • Koon Teo,
  • Katri Räikkönen,
  • Kari Stefansson,
  • Maria Molina-Vega,
  • Padmaja Subbarao,
  • Robin N. Beaumont,
  • Stefan Johansson,
  • Tiinamaija Tuomi,
  • Torben Hansen,
  • Line Engelbrechtsen,
  • Sonsoles Morcillo,
  • Emily Oken,
  • Elisabeth Quigstad,
  • Kåre I. Birkeland,
  • Marja Vääräsmäki,
  • Andrew T. Hattersley,
  • Sylvain Sebert,
  • Graham A. Hitman,
  • Soo Heon Kwak,
  • Marjo-Riitta Järvelin,
  • Rashmi B. Prasad,
  • Barbara Heude,
  • Aline Meirhaeghe,
  • Luigi Bouchard,
  • Pierre-Étienne Jacques,
  • Hannele Laivuori,
  • Kok Hian Tan,
  • Sonia S. Anand,
  • David A. van Heel,
  • Siyang Liu,
  • Pål R. Njølstad,
  • Valgerdur Steinthorsdottir,
  • Elisabeth Widén,
  • Elina Keikkala,
  • Denise M. Scholtens,
  • William L. Lowe,
  • Sarah Finer,
  • Andrew P. Morris,
  • Reedik Mägi,
  • Julia Zöllner,
  • Maria Carolina Borges,
  • Deborah A. Lawlor,
  • Marie-France Hivert,
  • Rachel M. Freathy,
  • David M. Evans,
  • Gunn-Helen Moen

摘要

Gestational diabetes mellitus (GDM) affects ~14% of pregnancies and increases maternal type 2 diabetes mellitus (T2DM) risk. The GenDiP Consortium presents 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 identify 37 GDM-associated loci (7 novel) and five novel loci for pregnancy glycemic traits, all operating through the maternal genome. We classify 12 GDM variants with stronger effects in GDM than T2DM into five biologically informed categories, revealing pleiotropy patterns, pregnancy-dependent effect modification, and diagnostic heterogeneity. While all these loci overlap with T2DM and/or non-pregnant glycaemic traits, four (G6PC2, CAST-PCSK1, HKDC1, FOXA2) lack genome-wide-significant T2DM associations; GCK shows distinct causal variants for GDM, and MTNR1B exhibits pregnancy-amplified effects. Our findings provide new genetic insights into GDM and highlight the need for larger, ancestrally diverse studies of GDM and glycaemic traits during pregnancy to understand potential pregnancy-specific effects.