Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0144531
Title: Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci
Authors: Reppe S.
Wang Y.
Thompson W.K.
McEvoy L.K.
Schork A.J.
Zuber V.
LeBlanc M.
Bettella F.
Mills I.G.
Desikan R.S.
Djurovic S.
Gautvik K.M.
Dale A.M.
Andreassen O.A.
Estrada K.
Styrkarsdottir U.
Evangelou E.
Hsu Y.-H.
Duncan E.L.
Ntzani E.E.
Oei L.
Albagha O.M.E.
Amin N.
Kemp J.P.
Koller D.L.
Li G.
Liu C.-T.
Minster R.L.
Moayyeri A.
Vandenput L.
Willner D.
Xiao S.-M.
Yerges-Armstrong L.M.
Zheng H.-F.
Alonso N.
Eriksson J.
Kammerer C.M.
Kaptoge S.K.
Leo P.J.
Thorleifsson G.
Wilson S.G.
Wilson J.F.
Aalto V.
Alen M.
Aragaki A.K.
Aspelund T.
Center J.R.
Dailiana Z.
Duggan D.J.
Garcia M.
Garcia-Giralt N.
Giroux S.
Hallmans G.
Hocking L.J.
Husted L.B.
Jameson K.A.
Khusainova R.
Kim G.S.
Kooperberg C.
Koromila T.
Kruk M.
Laaksonen M.
Lacroix A.Z.
Lee S.H.
Leung P.C.
Lewis J.R.
Masi L.
Mencej-Bedrac S.
Nguyen T.V.
Nogues X.
Patel M.S.
Prezelj J.
Rose L.M.
Scollen S.
Siggeirsdottir K.
Smith A.V.
Svensson O.
Trompet S.
Trummer O.
Van Schoor N.M.
Woo J.
Zhu K.
Balcells S.
Brandi M.L.
Buckley B.M.
Cheng S.
Christiansen C.
Cooper C.
Dedoussis G.
Ford I.
Frost M.
Goltzman D.
Gonz醠ez-Mac韆s J.
K鋒鰊en M.
Karlsson M.
Khusnutdinova E.
Koh J.-M.
Kollia P.
Langdahl B.L.
Leslie W.D.
Lips P.
Ljunggren �.
Lorenc R.S.
Marc J.
Mellstr鰉 D.
Obermayer-Pietsch B.
Olmos J.M.
Pettersson-Kymmer U.
Reid D.M.
Riancho J.A.
Ridker P.M.
Rousseau F.
Slagboom P.E.
Tang N.L.S.
Urreizti R.
Van Hul W.
Viikari J.
Zarrabeitia M.T.
Aulchenko Y.S.
Castano-Betancourt M.
Grundberg E.
Herrera L.
Ingvarsson T.
Johannsdottir H.
Kwan T.
Li R.
Luben R.
Medina-G髆ez C.
Palsson S.Th.
Rotter J.I.
Sigurdsson G.
Van Meurs J.B.J.
Verlaan D.
Williams F.M.K.
Wood A.R.
Zhou Y.
Pastinen T.
Raychaudhuri S.
Cauley J.A. 
Chasman D.I.
Clark G.R.
Cummings S.R.
Danoy P.
Dennison E.M.
Eastell R.
Eisman J.A.
Gudnason V.
Hofman A.
Jackson R.D.
Jones G.
Jukema J.W.
Khaw K.-T.
Lehtim鋕i T.
Liu Y.
Lorentzon M.
McCloskey E.
Mitchell B.D.
Nandakumar K.
Nicholson G.C.
Oostra B.A.
Peacock M.
Pols H.A.P.
Prince R.L.
Raitakari O.
Reid I.R.
Robbins J.
Sambrook P.N.
Sham P.C.
Shuldiner A.R.
Tylavsky F.A.
Van Duijn C.M.
Wareham N.J.
Cupples L.A.
Econs M.J.
Evans D.M.
Harris T.B.
Kung A.W.C.
Psaty B.M.
Reeve J.
Spector T.D.
Streeten E.A.
Zillikens M.C.
Thorsteinsdottir U.
Ohlsson C.
Karasik D.
Richards J.B.
Brown M.A.
Stefansson K.
Uitterlinden A.G.
Ralston S.H.
Ioannidis J.P.A.
Kiel D.P.
Rivadeneira F.
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
Issue Date: 2015
Citation: Reppe S., Wang Y., Thompson W.K., McEvoy L.K., Schork A.J., Zuber V., LeBlanc M., Bettella F., Mills I.G., Desikan R.S., Djurovic S., Gautvik K.M., Dale A.M., Andreassen O.A., Estrada K., Styrkarsdottir U., Evangelou E., Hsu Y.-H., Duncan E.L., Ntzani E.E., Oei L., Albagha O.M.E., Amin N., Kemp J.P., Koller D.L., Li G., Liu C.-T., Minster R.L., Moayyeri A., Vandenput L., Willner D., Xiao S.-M., Yerges-Armstrong L.M., Zheng H.-F., Alonso N., Eriksson J., Kammerer C.M., Kaptoge S.K., Leo P.J., Thorleifsson G., Wilson S.G., Wilson J.F., Aalto V., Alen M., Aragaki A.K., Aspelund T., Center J.R., Dailiana Z., Duggan D.J., Garcia M., Garcia-Giralt N., Giroux S., Hallmans G., Hocking L.J., Husted L.B., Jameson K.A., Khusainova R., Kim G.S., Kooperberg C., Koromila T., Kruk M., Laaksonen M., Lacroix A.Z., Lee S.H., Leung P.C., Lewis J.R., Masi L., Mencej-Bedrac S., Nguyen T.V., Nogues X., Patel M.S., Prezelj J., Rose L.M., Scollen S., Siggeirsdottir K., Smith A.V., Svensson O., Trompet S., Trummer O., Van Schoor N.M., Woo J., Zhu K., Balcells S., Brandi M.L., Buckley B.M., Cheng S., Christiansen C., Cooper C., Dedoussis G., Ford I., Frost M., Goltzman D., Gonz醠ez-Mac韆s J., K鋒鰊en M., Karlsson M., Khusnutdinova E., Koh J.-M., Kollia P., Langdahl B.L., Leslie W.D., Lips P., Ljunggren �., Lorenc R.S., Marc J., Mellstr鰉 D., Obermayer-Pietsch B., Olmos J.M., Pettersson-Kymmer U., Reid D.M., Riancho J.A., Ridker P.M., Rousseau F., Slagboom P.E., Tang N.L.S., Urreizti R., Van Hul W., Viikari J., Zarrabeitia M.T., Aulchenko Y.S., Castano-Betancourt M., Grundberg E., Herrera L., Ingvarsson T., Johannsdottir H., Kwan T., Li R., Luben R., Medina-G髆ez C., Palsson S.Th., Rotter J.I., Sigurdsson G., Van Meurs J.B.J., Verlaan D., Williams F.M.K., Wood A.R., Zhou Y., Pastinen T., Raychaudhuri S., Cauley J.A., Chasman D.I., Clark G.R., Cummings S.R., Danoy P., Dennison E.M., Eastell R., Eisman J.A., Gudnason V., Hofman A., Jackson R.D., Jones G., Jukema J.W., Khaw K.-T., Lehtim鋕i T., Liu Y., Lorentzon M., McCloskey E., Mitchell B.D., Nandakumar K., Nicholson G.C., Oostra B.A., Peacock M., Pols H.A.P., Prince R.L., Raitakari O., Reid I.R., Robbins J., Sambrook P.N., Sham P.C., Shuldiner A.R., Tylavsky F.A., Van Duijn C.M., Wareham N.J., Cupples L.A., Econs M.J., Evans D.M., Harris T.B., Kung A.W.C., Psaty B.M., Reeve J., Spector T.D., Streeten E.A., Zillikens M.C., Thorsteinsdottir U., Ohlsson C., Karasik D., Richards J.B., Brown M.A., Stefansson K., Uitterlinden A.G., Ralston S.H., Ioannidis J.P.A., Kiel D.P., Rivadeneira F. (2015). Genetic sharing with cardiovascular disease risk factors and diabetes reveals novel bone mineral density loci. PLoS ONE 10 (12) : e0144531. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0144531
Rights: Attribution 4.0 International
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.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161600
ISSN: 19326203
DOI: 10.1371/journal.pone.0144531
Rights: Attribution 4.0 International
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