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

Publication ,  Journal Article
Reppe, S; Wang, Y; Thompson, WK; McEvoy, LK; Schork, AJ; Zuber, V; LeBlanc, M; Bettella, F; Mills, IG; Desikan, RS; Djurovic, S; Gautvik, KM ...
Published in: PLoS One
2015

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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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2015

Volume

10

Issue

12

Start / End Page

e0144531

Location

United States

Related Subject Headings

  • Waist-Hip Ratio
  • Polymorphism, Single Nucleotide
  • Models, Genetic
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Pleiotropy
  • Genetic Loci
  • General Science & Technology
  • Gene Regulatory Networks
 

Citation

APA
Chicago
ICMJE
MLA
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Reppe, S., Wang, Y., Thompson, W. K., McEvoy, L. K., Schork, A. J., Zuber, V., … GEFOS Consortium, . (2015). Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. PLoS One, 10(12), e0144531. https://doi.org/10.1371/journal.pone.0144531
Reppe, Sjur, Yunpeng Wang, Wesley K. Thompson, Linda K. McEvoy, Andrew J. Schork, Verena Zuber, Marissa LeBlanc, et al. “Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.PLoS One 10, no. 12 (2015): e0144531. https://doi.org/10.1371/journal.pone.0144531.
Reppe S, Wang Y, Thompson WK, McEvoy LK, Schork AJ, Zuber V, et al. Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. PLoS One. 2015;10(12):e0144531.
Reppe, Sjur, et al. “Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.PLoS One, vol. 10, no. 12, 2015, p. e0144531. Pubmed, doi:10.1371/journal.pone.0144531.
Reppe S, Wang Y, Thompson WK, McEvoy LK, Schork AJ, Zuber V, LeBlanc M, Bettella F, Mills IG, Desikan RS, Djurovic S, Gautvik KM, Dale AM, Andreassen OA, GEFOS Consortium. Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci. PLoS One. 2015;10(12):e0144531.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2015

Volume

10

Issue

12

Start / End Page

e0144531

Location

United States

Related Subject Headings

  • Waist-Hip Ratio
  • Polymorphism, Single Nucleotide
  • Models, Genetic
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Pleiotropy
  • Genetic Loci
  • General Science & Technology
  • Gene Regulatory Networks