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., GEFOS Consortium, Willner, Dana, Duncan, Emma L, Leo, Paul J., Clark, Graeme R, Danoy, Patrick, Nicholson, Geoffrey C and Brown, Matthew A. (2015) Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci. PLoS ONE, 10 12: 0144531.1-0144531.20. doi:10.1371/journal.pone.0144531

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.
GEFOS Consortium
Willner, Dana
Duncan, Emma L
Leo, Paul J.
Clark, Graeme R
Danoy, Patrick
Nicholson, Geoffrey C
Brown, Matthew A.
Title Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-12-01
Sub-type Article (original research)
DOI 10.1371/journal.pone.0144531
Open Access Status DOI
Volume 10
Issue 12
Start page 0144531.1
End page 0144531.20
Total pages 20
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 4 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 01 Mar 2016, 12:12:49 EST by System User on behalf of Learning and Research Services (UQ Library)