@article{3056830,
    title = "Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci",
    author = "Reppe, S. and Wang, Y. and Thompson, W.K. and McEvoy, L.K. and Schork, A.J. and Zuber, V. and LeBlanc, M. and Bettella, F. and Mills, I.G. and Desikan, R.S. and Djurovic, S. and Gautvik, K.M. and Dale, A.M. and Andreassen, O.A. and Estrada, K. and Styrkarsdottir, U. and Evangelou, E. and Hsu, Y.-H. and Duncan, E.L. and Ntzani, E.E. and Oei, L. and Albagha, O.M.E. and Amin, N. and Kemp, J.P. and Koller, D.L. and Li, G. and Liu, C.-T. and Minster, R.L. and Moayyeri, A. and Vandenput, L. and Willner, D. and Xiao, S.-M. and Yerges-Armstrong, L.M. and Zheng, H.-F. and Alonso, N. and Eriksson, J. and Kammerer, C.M. and Kaptoge, S.K. and Leo, P.J. and Thorleifsson, G. and Wilson, S.G. and Wilson, J.F. and Aalto, V. and Alen, M. and Aragaki, A.K. and Aspelund, T. and Center, J.R. and Dailiana, Z. and Duggan, D.J. and Garcia, M. and Garcia-Giralt, N. and Giroux, S. and Hallmans, G. and Hocking, L.J. and Husted, L.B. and Jameson, K.A. and Khusainova, R. and Kim, G.S. and Kooperberg, C. and Koromila, T. and Kruk, M. and Laaksonen, M. and Lacroix, A.Z. and Lee, S.H. and Leung, P.C. and Lewis, J.R. and Masi, L. and Mencej-Bedrac, S. and Nguyen, T.V. and Nogues, X. and Patel, M.S. and Prezelj, J. and Rose, L.M. and Scollen, S. and Siggeirsdottir, K. and Smith, A.V. and Svensson, O. and Trompet, S. and Trummer, O. and Van Schoor, N.M. and Woo, J. and Zhu, K. and Balcells, S. and Brandi, M.L. and Buckley, B.M. and Cheng, S. and Christiansen, C. and Cooper, C. and Dedoussis, G. and Ford, I. and Frost, M. and Goltzman, D. and González-Macías, J. and Kähönen, M. and Karlsson, M. and Khusnutdinova, E. and Koh, J.-M. and Kollia, P. and Langdahl, B.L. and Leslie, W.D. and Lips, P. and Ljunggren, Ö. and Lorenc, R.S. and Marc, J. and Mellström, D. and Obermayer-Pietsch, B. and Olmos, J.M. and Pettersson-Kymmer, U. and Reid, D.M. and Riancho, J.A. and Ridker, P.M. and Rousseau, F. and Slagboom, P.E. and Tang, N.L.S. and Urreizti, R. and Van Hul, W. and Viikari, J. and Zarrabeitia, M.T. and Aulchenko, Y.S. and Castano-Betancourt, M. and Grundberg, E. and Herrera, L. and Ingvarsson, T. and Johannsdottir, H. and Kwan, T. and Li, R. and Luben, R. and Medina-Gómez, C. and Palsson, S.Th. and Rotter, J.I. and Sigurdsson, G. and Van Meurs, J.B.J. and Verlaan, D. and Williams, F.M.K. and Wood, A.R. and Zhou, Y. and Pastinen, T. and Raychaudhuri, S. and Cauley, J.A. and Chasman, D.I. and Clark, G.R. and Cummings, S.R. and Danoy, P. and Dennison, E.M. and Eastell, R. and Eisman, J.A. and Gudnason, V. and Hofman, A. and Jackson, R.D. and Jones, G. and Jukema, J.W. and Khaw, K.-T. and Lehtimäki, T. and Liu, Y. and Lorentzon, M. and McCloskey, E. and Mitchell, B.D. and Nandakumar, K. and Nicholson, G.C. and Oostra, B.A. and Peacock, M. and Pols, H.A.P. and Prince, R.L. and Raitakari, O. and Reid, I.R. and Robbins, J. and Sambrook, P.N. and Sham, P.C. and Shuldiner, A.R. and Tylavsky, F.A. and Van Duijn, C.M. and Wareham, N.J. and Cupples, L.A. and Econs, M.J. and Evans, D.M. and Harris, T.B. and Kung, A.W.C. and Psaty, B.M. and Reeve, J. and Spector, T.D. and Streeten, E.A. and Zillikens, M.C. and Thorsteinsdottir, U. and Ohlsson, C. and Karasik, D. and Richards, J.B. and Brown, M.A. and Stefansson, K. and Uitterlinden, A.G. and Ralston, S.H. and Ioannidis, J.P.A. and Kiel, D.P. and Rivadeneira, F. and GEFOS Consortium",
    journal = "PLOS ONE",
    year = "2015",
    volume = "10",
    number = "12",
    publisher = "Public Library of Science",
    doi = "10.1371/journal.pone.0144531",
    keywords = "high density lipoprotein;  low density lipoprotein;  triacylglycerol, Article;  bone density;  bone metabolism;  cardiovascular disease;  cardiovascular risk;  cell lineage;  comorbidity;  diabetes mellitus;  diastolic blood pressure;  gene expression;  gene locus;  genetic association;  genetic risk;  genetic variability;  human;  insulin dependent diabetes mellitus;  non insulin dependent diabetes mellitus;  osteoblast;  osteocyte;  pleiotropy;  risk assessment;  signal transduction;  single nucleotide polymorphism;  systolic blood pressure;  waist hip ratio;  biological model;  cardiovascular disease;  gene locus;  gene regulatory network;  genetic predisposition;  genetics;  genome-wide association study;  single nucleotide polymorphism, Bone Density;  Cardiovascular Diseases;  Diabetes Mellitus, Type 1;  Diabetes Mellitus, Type 2;  Gene Regulatory Networks;  Genetic Loci;  Genetic Pleiotropy;  Genetic Predisposition to Disease;  Genome-Wide Association Study;  Humans;  Models, Genetic;  Polymorphism, Single Nucleotide;  Waist-Hip Ratio",
    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. © 2015 Reppe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited."
}