DOCUMENT
1/1
Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Implicated Through Clustering
figure
posted on 2020-10-13, 15:20 authored by Ada AdminAda Admin, Camille E. Powe, Miriam S. Udler, Sarah Hsu, Catherine Allard, Alan Kuang, Alisa K. Manning, Patrice Perron, Luigi Bouchard, William L. Lowe Jr, Denise Scholtens, Jose C. Florez, Marie-France HivertHundreds
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 (GDM) is distinct from that underlying T2D. In
this study of over 5,000 pregnant women from three cohorts, we aimed to
identify physiologically related groups of maternal variants associated with GDM
using two complementary approaches based on Bayesian non-negative matrix
factorization (bNMF) clustering. First, we tested five bNMF clusters of
maternal T2D-associated variants grouped based on physiology outside of
pregnancy for association with GDM. We found that cluster polygenic scores representing
genetic determinants of reduced beta-cell function and abnormal hepatic lipid
metabolism were associated with GDM; these clusters were not associated with
infant birthweight. Second, we derived bNMF clusters of maternal variants based
on pregnancy physiology and tested these clusters for association with GDM. We identified a cluster which was strongly associated with
GDM and also associated with higher infant birthweight. 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.