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Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci

Reppe, Sjur and Andreassen, Ole A. (2015) In PLoS ONE 10(12).
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,... (More)

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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type
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publication status
published
subject
in
PLoS ONE
volume
10
issue
12
article number
e0144531
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:84958012773
  • pmid:26695485
ISSN
1932-6203
DOI
10.1371/journal.pone.0144531
language
English
LU publication?
yes
id
c9640ec2-0f0e-4a00-a6b4-dc7dbfce607a
date added to LUP
2019-05-22 19:12:58
date last changed
2024-07-23 18:31:17
@article{c9640ec2-0f0e-4a00-a6b4-dc7dbfce607a,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Reppe, Sjur and Andreassen, Ole A.}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{12}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0144531}},
  doi          = {{10.1371/journal.pone.0144531}},
  volume       = {{10}},
  year         = {{2015}},
}