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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.
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.
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.
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.
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.
Keywords
Date
2015
Type
Journal article
Journal
PLoS ONE
Book
Volume
10
Issue
12
Page Range
1-20
Article Number
Article e0144531
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
CC BY 4.0
File Access
Open