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DOI 10.1038/s41467-026-73509-y

Медицинская библиотека · Nature communications · 2026

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

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

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Аннотация

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.

Для цитирования: Brito Nunes Caroline, Rukins Valentina, Cisse Aminata H, White Frédérique, McBride Nancy, Kuang Alan, Allard Catherine, Ronkainen Justiina, Hughes Alice, Elliott Amanda, Thorleifsson Gudmar, Vaudel Marc, Laisk Triin, Gu Yuqin, Lamri Amel, Chen Li, Tuhkanen Johanna, Lahti Jari, Calas Lucinda, Muntaner Manon, Karhunen Ville, Choi Jaewon, Heiskala Anni, Hatem Gad, Fragoso-Bargas Nicolas, Rifas-Shiman Sheryl L, Paz-Lopez Guillermo, Stinson Sara E, Bhowmik Bishwajit, Ahlqvist Emma, Estonian Biobank Research Team, Genes & Health Research Team, Deleuze Jean-Francois, Eriksson Johan G, Park Jongseok, Teo Koon, Räikkönen Katri, Stefansson Kari, Molina-Vega Maria, Subbarao Padmaja, Beaumont Robin N, Johansson Stefan, Tuomi Tiinamaija, Hansen Torben, Engelbrechtsen Line, Morcillo Sonsoles, Oken Emily, Quigstad Elisabeth, Birkeland Kåre I, Vääräsmäki Marja, Hattersley Andrew T, Sebert Sylvain, Hitman Graham A, Kwak Soo Heon, Järvelin Marjo-Riitta, Prasad Rashmi B, Heude Barbara, Meirhaeghe Aline, Bouchard Luigi, Jacques Pierre-Étienne, Laivuori Hannele, Tan Kok Hian, Anand Sonia S, van Heel David A, Liu Siyang, Njølstad Pål R, Steinthorsdottir Valgerdur, Widén Elisabeth, Keikkala Elina, Scholtens Denise M, Lowe William L, Finer Sarah, Morris Andrew P, Mägi Reedik, Zöllner Julia, Borges Maria Carolina, Lawlor Deborah A, Hivert Marie-France, Freathy Rachel M, Evans David M, Moen Gunn-Helen. Multi-ancestry, trans-generational GWAS meta-analysis of gestational diabetes and glycaemic traits during pregnancy reveals limited evidence of pregnancy-specific genetic effects.. Nature communications. 2026. DOI: 10.1038/s41467-026-73509-y.

Предметные рубрики MeSH

Genome-Wide Association StudyFemaleDiabetes, GestationalHumansPregnancyDiabetes Mellitus, Type 2Genetic Predisposition to DiseasePolymorphism, Single NucleotideBlood GlucoseReceptor, Melatonin, MT2
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