A landmark genetic study on gestational diabetes has led to the discovery of nine new genetic regions that are associated with this severe and common pregnancy complication. The results shed light on previously unknown physiological mechanisms related to the development of diabetes, including adaptive changes in the brain during pregnancy.
A new study led by researchers from the University of Helsinki, along with colleagues from the Massachusetts General Hospital and the Broad Institute of Harvard and MIT, has achieved significant breakthroughs in understanding the genetics behind gestational diabetes.
Gestational diabetes is a common pregnancy disorder that affects more than 16 million pregnancies worldwide each year, with significant health implications for both mothers and their children. It is characterized by elevated blood sugar levels in pregnant women who did not have diabetes before pregnancy.
Despite gestational diabetes being a major global health problem, there is remarkably little research on its molecular causes.
The study, published in Nature Genetics, is the largest genome-wide association study on gestational diabetes, involving more than 12,000 patients and 131,000 female controls from the Finnish Genomics Initiative FinnGen.
This groundbreaking research has nearly tripled the number of known genetic regions associated with gestational diabetes, identifying a total of 13 different chromosomal regions linked to the condition.
Using recently developed analysis methods, the researchers demonstrated that there are two different classes of genetic variants associated with gestational diabetes: those that are shared with type 2 diabetes, and those that are predominantly linked to the pregnancy form of diabetes.
„Our findings suggest that gestational diabetes has a unique genetic basis that partially differs from type 2 diabetes, calling into question earlier assumptions about the common genetic basis of the two conditions,“ said Dr. Elisabeth Widén of the Institute for Molecular Medicine Finland (FIMM), University of Helsinki, who led the study.
The study’s results also provide crucial insights into possible physiological mechanisms related to the development of diabetes during pregnancy. These mechanisms include adaptive changes in the brain and altered insulin sensitivity in the mother. The hypothalamus emerged as a focal point, with some of the identified risk genes being active in brain cell types known to be important for adaptive responses to maintain blood sugar regulation during pregnancy.
„Biobank-based studies like FinnGen with comprehensive and lifelong clinical data enable large-scale studies on many women’s and reproductive health phenotypes, which have lacked research funding until now,“ said Dr. Mark Daly, former director of FIMM and a geneticist at the Massachusetts General Hospital and the Broad Institute, who jointly supervised the study. „It’s exciting to see how this work is bearing fruit for important and understudied diseases.“
While the study primarily focused on a Finnish population, the results have broader implications. Most risk variants are common, underscoring the potential relevance of these findings for various population groups at risk for gestational diabetes.
The work sheds light on a very common pregnancy disorder that has been poorly researched for years and is highly relevant to women’s health in general. Furthermore, the results improve the overall understanding of glucose metabolism dysregulation.
„By providing novel data on critical genetic factors and signaling pathways, our study has the potential to transform not only attitudes and approaches toward gestational diabetes research, but also research aimed at pregnancy-related health outcomes overall, ultimately benefiting the health of mothers and their newborns.“
Dr. Elisabeth Widén of the Institute for Molecular Medicine Finland (FIMM), University of Helsinki
University of Helsinki
Elliott, A., et al. (2024). Distinct and shared genetic architectures of gestational diabetes mellitus and type 2 diabetes. Nature Genetics. doi.org/10.1038/s41588-023-01607-4.