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Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a nov...

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Autores principales: Reppe, Sjur, Wang, Yunpeng, Thompson, Wesley K., McEvoy, Linda K., Schork, Andrew J., Zuber, Verena, LeBlanc, Marissa, Bettella, Francesco, Mills, Ian G., Desikan, Rahul S., Djurovic, Srdjan, Gautvik, Kaare M., Dale, Anders M., Andreassen, Ole A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687843/
https://www.ncbi.nlm.nih.gov/pubmed/26695485
http://dx.doi.org/10.1371/journal.pone.0144531
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author Reppe, Sjur
Wang, Yunpeng
Thompson, Wesley K.
McEvoy, Linda K.
Schork, Andrew J.
Zuber, Verena
LeBlanc, Marissa
Bettella, Francesco
Mills, Ian G.
Desikan, Rahul S.
Djurovic, Srdjan
Gautvik, Kaare M.
Dale, Anders M.
Andreassen, Ole A.
author_facet Reppe, Sjur
Wang, Yunpeng
Thompson, Wesley K.
McEvoy, Linda K.
Schork, Andrew J.
Zuber, Verena
LeBlanc, Marissa
Bettella, Francesco
Mills, Ian G.
Desikan, Rahul S.
Djurovic, Srdjan
Gautvik, Kaare M.
Dale, Anders M.
Andreassen, Ole A.
author_sort Reppe, Sjur
collection PubMed
description Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.
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spelling pubmed-46878432015-12-31 Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci Reppe, Sjur Wang, Yunpeng Thompson, Wesley K. McEvoy, Linda K. Schork, Andrew J. Zuber, Verena LeBlanc, Marissa Bettella, Francesco Mills, Ian G. Desikan, Rahul S. Djurovic, Srdjan Gautvik, Kaare M. Dale, Anders M. Andreassen, Ole A. PLoS One Research Article Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity. Public Library of Science 2015-12-22 /pmc/articles/PMC4687843/ /pubmed/26695485 http://dx.doi.org/10.1371/journal.pone.0144531 Text en © 2015 Reppe et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Reppe, Sjur
Wang, Yunpeng
Thompson, Wesley K.
McEvoy, Linda K.
Schork, Andrew J.
Zuber, Verena
LeBlanc, Marissa
Bettella, Francesco
Mills, Ian G.
Desikan, Rahul S.
Djurovic, Srdjan
Gautvik, Kaare M.
Dale, Anders M.
Andreassen, Ole A.
Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci
title Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci
title_full Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci
title_fullStr Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci
title_full_unstemmed Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci
title_short Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci
title_sort genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687843/
https://www.ncbi.nlm.nih.gov/pubmed/26695485
http://dx.doi.org/10.1371/journal.pone.0144531
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