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https://doi.org/10.1371/journal.pone.0144531
Title: | Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci | Authors: | Reppe S. Wang Y. Thompson W.K. McEvoy L.K. Schork A.J. Zuber V. LeBlanc M Bettella F. Mills I.G. Desikan R.S. Djurovic S. Gautvik K.M. Dale A.M. Andreassen O.A. GEFOS Consortium |
Keywords: | high density lipoprotein low density lipoprotein triacylglycerol Article bone density bone metabolism cardiovascular disease cardiovascular risk cell lineage comorbidity diabetes mellitus diastolic blood pressure gene expression gene locus genetic association genetic risk genetic variability human insulin dependent diabetes mellitus non insulin dependent diabetes mellitus osteoblast osteocyte pleiotropy risk assessment signal transduction single nucleotide polymorphism systolic blood pressure waist hip ratio biological model cardiovascular disease gene locus gene regulatory network genetic predisposition genetics genome-wide association study single nucleotide polymorphism Bone Density Cardiovascular Diseases Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Gene Regulatory Networks Genetic Loci Genetic Pleiotropy Genetic Predisposition to Disease Genome-Wide Association Study Humans Models, Genetic Polymorphism, Single Nucleotide Waist-Hip Ratio |
Issue Date: | 2015 | Citation: | Reppe S., Wang Y., Thompson W.K., McEvoy L.K., Schork A.J., Zuber V., LeBlanc M, Bettella F., Mills I.G., Desikan R.S., Djurovic S., Gautvik K.M., Dale A.M., Andreassen O.A., GEFOS Consortium (2015). Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci. PLoS ONE 10 (12) : e0144531. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0144531 | Rights: | Attribution 4.0 International | Abstract: | 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. © 2015 Reppe et al. 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 credited. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161600 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0144531 | Rights: | Attribution 4.0 International |
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