@article{10902/31297,
year = {2015},
url = {https://hdl.handle.net/10902/31297},
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.},
organization = {This work was supported by the Research Council of Norway [grant number 183782/V50 to OAA]; the South East Norway Health Authority [grant number 2010-074 to OAA and 52009/8029 to KMG]; the National Institutes of Health [grant number T32 EB005970 to RSD, RC2DA029475 and R01HD061414 to AJS]; the Robert J. Glushko and Pamela Samuelson Graduate Fellowship to AJS; the 6th EU framework program [grant number LSHM-CT-2003-502941 to KMG and SR]; and Oslo University Hospital, Ullevaal [grant number 52009/8029 to KMG]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.},
publisher = {PLoS One, 2015, 10(12),  e0144531},
title = {Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci},
author = {Reppe, Sjur and Wang, Yunpeng and Thompson, Wesley K. and McEvoy, Linda K. and Schork, Andrew J. and Zuber, Verena and LeBlanc, Marissa and Bettella, Francesco and Mills, Ian G. and Desikan, Rahul S. and Djurovic, Srdjan and Gautvik, Kaare M. and Dale, Anders M. and Andreassen, Ole A. and González Macías, Jesús and Olmos Martínez, José Manuel and Riancho Moral, José Antonio and Zarrabeitia Cimiano, María Teresa},
}