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- Title
Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering.
- Authors
Powe, Camille E.; Udler, Miriam S.; Hsu, Sarah; Allard, Catherine; Kuang, Alan; Manning, Alisa K.; Perron, Patrice; Bouchard, Luigi; Lowe Jr., William L.; Scholtens, Denise; Florez, Jose C.; Hivert, Marie-France; Lowe, William L Jr
- Abstract
Hundreds of common genetic variants acting through distinguishable physiologic pathways influence the risk of type 2 diabetes (T2D). It is unknown to what extent the physiology underlying gestational diabetes mellitus (GDM) is distinct from that underlying T2D. In this study of >5,000 pregnant women from three cohorts, we aimed to identify physiologically related groups of maternal variants associated with GDM using two complementary approaches that were based on Bayesian nonnegative matrix factorization (bNMF) clustering. First, we tested five bNMF clusters of maternal T2D-associated variants grouped on the basis of physiology outside of pregnancy for association with GDM. We found that cluster polygenic scores representing genetic determinants of reduced β-cell function and abnormal hepatic lipid metabolism were associated with GDM; these clusters were not associated with infant birth weight. Second, we derived bNMF clusters of maternal variants on the basis of pregnancy physiology and tested these clusters for association with GDM. We identified a cluster that was strongly associated with GDM as well as associated with higher infant birth weight. The effect size for this cluster's association with GDM appeared greater than that for T2D. Our findings imply that the genetic and physiologic pathways that lead to GDM differ, at least in part, from those that lead to T2D.
- Subjects
GESTATIONAL diabetes; TYPE 2 diabetes; WEIGHT in infancy; BIRTH weight; MATRIX decomposition; RESEARCH; RESEARCH methodology; GENETIC polymorphisms; GENETIC disorders; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; GENOMES; DISEASE susceptibility; GENOTYPES; RESEARCH funding; CLUSTER analysis (Statistics); LIPID metabolism disorders
- Publication
Diabetes, 2021, Vol 70, Issue 1, p268
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db20-0772