Distinct and shared genetic architectures of gestational diabetes mellitus and type 2 diabetes

Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting more than 16 million pregnancies annually worldwide 1 , 2 . GDM is related to an increased lifetime risk of type 2 diabetes (T2D) 1 – 3 , with over a third of women developing T2D within 15 years of their GDM diagnosis. The...

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Vydáno v:Nature genetics Ročník 56; číslo 3; s. 377 - 382
Hlavní autoři: Elliott, Amanda, Walters, Raymond K., Pirinen, Matti, Kurki, Mitja, Junna, Nella, Goldstein, Jacqueline I., Reeve, Mary Pat, Siirtola, Harri, Lemmelä, Susanna M., Turley, Patrick, Lahtela, Elisa, Mehtonen, Juha, Reis, Kadri, Elnahas, Abdelrahman G., Reigo, Anu, Palta, Priit, Esko, Tõnu, Mägi, Reedik, Palotie, Aarno, Daly, Mark J., Widén, Elisabeth
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York Nature Publishing Group US 01.03.2024
Nature Publishing Group
Témata:
631/208/205/2138
692/699/2743/137/1926
692/699/2743/137/773
Agriculture
Animal Genetics and Genomics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Diabetes Mellitus, Type 2 - genetics
Diabetes, Gestational - genetics
Etiology
Female
Gene expression
Gene Function
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Gestational diabetes
Glucose
Health risk assessment
Homeostasis
Human Genetics
Humans
Islet cells
Islets of Langerhans
Letter
Metabolic disorders
Placenta
Pregnancy
Pregnancy complications
Risk
Steroidogenesis
Womens health
ISSN:1061-4036, 1546-1718, 1546-1718
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Shrnutí:Gestational diabetes mellitus (GDM) is a common metabolic disorder affecting more than 16 million pregnancies annually worldwide 1 , 2 . GDM is related to an increased lifetime risk of type 2 diabetes (T2D) 1 – 3 , with over a third of women developing T2D within 15 years of their GDM diagnosis. The diseases are hypothesized to share a genetic predisposition 1 – 7 , but few studies have sought to uncover the genetic underpinnings of GDM. Most studies have evaluated the impact of T2D loci only 8 – 10 , and the three prior genome-wide association studies of GDM 11 – 13 have identified only five loci, limiting the power to assess to what extent 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 nine new 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 the following 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. Genome-wide association analyses identify 13 loci associated with gestational diabetes, showing partial overlap with type 2 diabetes risk loci but also distinct genetic architecture predominantly influencing pregnancy-related mechanisms.
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ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/s41588-023-01607-4