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

Journal article


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. and Andreassen, Ole A.. (2015). Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci. PLoS ONE. 10(12), p. Article: e0144531. https://doi.org/10.1371/journal.pone.0144531
AuthorsReppe, 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. and 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.

Year2015
JournalPLoS ONE
Journal citation10 (12), p. Article: e0144531
PublisherPublic Library of Science
ISSN1932-6203
Digital Object Identifier (DOI)https://doi.org/10.1371/journal.pone.0144531
PubMed ID26695485
Scopus EID2-s2.0-84958012773
PubMed Central IDPMC4687843
Open accessPublished as ‘gold’ (paid) open access
Research or scholarlyResearch
Page range1-20
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online22 Dec 2015
Publication process dates
Accepted19 Nov 2015
Deposited11 Nov 2021
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https://acuresearchbank.acu.edu.au/item/8x088/genetic-sharing-with-cardiovascular-disease-risk-factors-and-diabetes-reveals-novel-bone-mineral-density-loci

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