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Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering

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 wo...

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Autores principales: Powe, Camille E., Udler, Miriam S., Hsu, Sarah, Allard, Catherine, Kuang, Alan, Manning, Alisa K., Perron, Patrice, Bouchard, Luigi, Lowe, William L., Scholtens, Denise, Florez, Jose C., Hivert, Marie-France
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876560/
https://www.ncbi.nlm.nih.gov/pubmed/33051273
http://dx.doi.org/10.2337/db20-0772
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author Powe, Camille E.
Udler, Miriam S.
Hsu, Sarah
Allard, Catherine
Kuang, Alan
Manning, Alisa K.
Perron, Patrice
Bouchard, Luigi
Lowe, William L.
Scholtens, Denise
Florez, Jose C.
Hivert, Marie-France
author_facet Powe, Camille E.
Udler, Miriam S.
Hsu, Sarah
Allard, Catherine
Kuang, Alan
Manning, Alisa K.
Perron, Patrice
Bouchard, Luigi
Lowe, William L.
Scholtens, Denise
Florez, Jose C.
Hivert, Marie-France
author_sort Powe, Camille E.
collection PubMed
description 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.
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spelling pubmed-78765602022-01-01 Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering Powe, Camille E. Udler, Miriam S. Hsu, Sarah Allard, Catherine Kuang, Alan Manning, Alisa K. Perron, Patrice Bouchard, Luigi Lowe, William L. Scholtens, Denise Florez, Jose C. Hivert, Marie-France Diabetes Genetics/Genomes/Proteomics/Metabolomics 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. American Diabetes Association 2021-01 2020-10-13 /pmc/articles/PMC7876560/ /pubmed/33051273 http://dx.doi.org/10.2337/db20-0772 Text en © 2020 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Genetics/Genomes/Proteomics/Metabolomics
Powe, Camille E.
Udler, Miriam S.
Hsu, Sarah
Allard, Catherine
Kuang, Alan
Manning, Alisa K.
Perron, Patrice
Bouchard, Luigi
Lowe, William L.
Scholtens, Denise
Florez, Jose C.
Hivert, Marie-France
Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering
title Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering
title_full Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering
title_fullStr Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering
title_full_unstemmed Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering
title_short Genetic Loci and Physiologic Pathways Involved in Gestational Diabetes Mellitus Implicated Through Clustering
title_sort genetic loci and physiologic pathways involved in gestational diabetes mellitus implicated through clustering
topic Genetics/Genomes/Proteomics/Metabolomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876560/
https://www.ncbi.nlm.nih.gov/pubmed/33051273
http://dx.doi.org/10.2337/db20-0772
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