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Endocrine
Published in: Endocrine 2/2023

Open Access 27-12-2022 | Original Article

Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children

Authors: Jiawen Xu, Jun Ma, Yi Zeng, Haibo Si, Yuangang Wu, Shaoyun Zhang, Bin Shen

Published in: Endocrine | Issue 2/2023

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Abstract

Objective

To identify novel candidate genes whose expression is associated with bone mineral density (BMD) and body lean mass (LM) in children.

Methods

A tissue-specific transcriptome-wide association study (TWAS) was conducted utilizing a large-scale genome-wide association study (GWAS) dataset associated with BMD and LM and involving 10,414 participants. The measurement of BMD and LM phenotypes was made based on total-body dual-energy X-ray absorptiometry (TB-DXA) scans. TWAS was conducted by using FUSION software. Reference panels for muscle skeleton (MS), peripheral blood (NBL) and whole blood (YBL) were used for TWAS analysis. Functional enrichment and protein–protein interaction (PPI) analyses of the genes identified by TWAS were performed by using the online tool Metascape (http://​metascape.​org).

Results

For BMD, we identified 174 genes with P < 0.05, such as IKZF1 (P = 1.46 × 10−9) and CHKB (P = 8.31 × 10−7). For LM, we identified 208 genes with P < 0.05, such as COPS5 (P = 3.03 × 10−12) and MRPS33 (P = 5.45 × 10−10). Gene ontology (GO) enrichment analysis of the BMD-associated genes revealed 200 GO terms, such as protein catabolic process (Log P = −5.09) and steroid hormone-mediated signaling pathway (Log P = −3.13). GO enrichment analysis of the LM-associated genes detected 287 GO terms, such as the apoptotic signaling pathway (Log P = −8.08) and lipid storage (Log P = −3.55).

Conclusion

This study identified several candidate genes for BMD and LM in children, providing novel clues to the genetic mechanisms underlying the development of childhood BMD and LM.
Literature
1.
S.M. Knight, E.F. Ring, A.K. Bhalla, Bone mineral density and osteoarthritis. Ann. Rheum. Dis. 51(9), 1025–1026 (1992)CrossRef
2.
S.M. Ribeiro, J.J. Kehayias, Sarcopenia and the analysis of body composition. Adv. Nutr. (Bethesda. Md) 5(3), 260–267 (2014)
3.
H.F. Ip, R. Jansen, A. Abdellaoui, M. Bartels, D.I. Boomsma, M.G. Nivard, Characterizing the relation between expression QTLs and complex traits: exploring the role of tissue specificity. Behav. Genet. 48(5), 374–385 (2018)CrossRef
4.
J. Lutz, R. Tesar, Mother-daughter pairs: spinal and femoral bone densities and dietary intakes. Am. J. Clin. Nutr. 52(5), 872–877 (1990)CrossRef
5.
U. Styrkarsdottir, G. Thorleifsson, S.A. Gudjonsson, A. Sigurdsson, J.R. Center, S.H. Lee, T.V. Nguyen, T.C.Y. Kwok, J.S.W. Lee, S.C. Ho, J. Woo, P.C. Leung, B.J. Kim, T. Rafnar, L.A. Kiemeney, T. Ingvarsson, J.M. Koh, N.L.S. Tang, J.A. Eisman, C. Christiansen, G. Sigurdsson, U. Thorsteinsdottir, K. Stefansson, Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures. Nat. Commun. 7, 10129 (2016)CrossRef
6.
H.F. Zheng, V. Forgetta, Y.H. Hsu, K. Estrada, A. Rosello-Diez, P.J. Leo, C.L. Dahia, K.H. Park-Min, J.H. Tobias, C. Kooperberg, A. Kleinman, U. Styrkarsdottir, C.T. Liu, C. Uggla, D.S. Evans, C.M. Nielson, K. Walter, U. Pettersson-Kymmer, S. McCarthy, J. Eriksson, T. Kwan, M. Jhamai, K. Trajanoska, Y. Memari, J. Min, J. Huang, P. Danecek, B. Wilmot, R. Li, W.C. Chou, L.E. Mokry, A. Moayyeri, M. Claussnitzer, C.H. Cheng, W. Cheung, C. Medina-Gómez, B. Ge, S.H. Chen, K. Choi, L. Oei, J. Fraser, R. Kraaij, M.A. Hibbs, C.L. Gregson, D. Paquette, A. Hofman, C. Wibom, G.J. Tranah, M. Marshall, B.B. Gardiner, K. Cremin, P. Auer, L. Hsu, S. Ring, J.Y. Tung, G. Thorleifsson, A.W. Enneman, N.M. van Schoor, L.C. de Groot, N. van der Velde, B. Melin, J.P. Kemp, C. Christiansen, A. Sayers, Y. Zhou, S. Calderari, J. van Rooij, C. Carlson, U. Peters, S. Berlivet, J. Dostie, A.G. Uitterlinden, S.R. Williams, C. Farber, D. Grinberg, A.Z. LaCroix, J. Haessler, D.I. Chasman, F. Giulianini, L.M. Rose, P.M. Ridker, J.A. Eisman, T.V. Nguyen, J.R. Center, X. Nogues, N. Garcia-Giralt, L.L. Launer, V. Gudnason, D. Mellström, L. Vandenput, N. Amin, C.M. van Duijn, M.K. Karlsson, Ö. Ljunggren, O. Svensson, G. Hallmans, F. Rousseau, S. Giroux, J. Bussière, P.P. Arp, F. Koromani, R.L. Prince, J.R. Lewis, B.L. Langdahl, A.P. Hermann, J.E. Jensen, S. Kaptoge, K.T. Khaw, J. Reeve, M.M. Formosa, A. Xuereb-Anastasi, K. Åkesson, F.E. McGuigan, G. Garg, J.M. Olmos, M.T. Zarrabeitia, J.A. Riancho, S.H. Ralston, N. Alonso, X. Jiang, D. Goltzman, T. Pastinen, E. Grundberg, D. Gauguier, E.S. Orwoll, D. Karasik, G. Davey-Smith, A.V. Smith, K. Siggeirsdottir, T.B. Harris, M.C. Zillikens, J.B. van Meurs, U. Thorsteinsdottir, M.T. Maurano, N.J. Timpson, N. Soranzo, R. Durbin, S.G. Wilson, E.E. Ntzani, M.A. Brown, K. Stefansson, D.A. Hinds, T. Spector, L.A. Cupples, C. Ohlsson, C.M. Greenwood, R.D. Jackson, D.W. Rowe, C.A. Loomis, D.M. Evans, C.L. Ackert-Bicknell, A.L. Joyner, E.L. Duncan, D.P. Kiel, F. Rivadeneira, J.B. Richards, Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 526(7571), 112–117 (2015)CrossRef
7.
F. Rivadeneira, U. Styrkársdottir, K. Estrada, B.V. Halldórsson, Y.H. Hsu, J.B. Richards, M.C. Zillikens, F.K. Kavvoura, N. Amin, Y.S. Aulchenko, L.A. Cupples, P. Deloukas, S. Demissie, E. Grundberg, A. Hofman, A. Kong, D. Karasik, J.B. van Meurs, B. Oostra, T. Pastinen, H.A. Pols, G. Sigurdsson, N. Soranzo, G. Thorleifsson, U. Thorsteinsdottir, F.M. Williams, S.G. Wilson, Y. Zhou, S.H. Ralston, C.M. van Duijn, T. Spector, D.P. Kiel, K. Stefansson, J.P. Ioannidis, A.G. Uitterlinden, Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat. Genet. 41(11), 1199–1206 (2009)CrossRef
8.
J.B. Richards, F. Rivadeneira, M. Inouye, T.M. Pastinen, N. Soranzo, S.G. Wilson, T. Andrew, M. Falchi, R. Gwilliam, K.R. Ahmadi, A.M. Valdes, P. Arp, P. Whittaker, D.J. Verlaan, M. Jhamai, V. Kumanduri, M. Moorhouse, J.B. van Meurs, A. Hofman, H.A. Pols, D. Hart, G. Zhai, B.S. Kato, B.H. Mullin, F. Zhang, P. Deloukas, A.G. Uitterlinden, T.D. Spector, Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371(9623), 1505–1512 (2008)CrossRef
9.
K. Estrada, U. Styrkarsdottir, E. Evangelou, Y.H. Hsu, E.L. Duncan, E.E. Ntzani, L. Oei, O.M. Albagha, N. Amin, J.P. Kemp, D.L. Koller, G. Li, C.T. Liu, R.L. Minster, A. Moayyeri, L. Vandenput, D. Willner, S.M. Xiao, L.M. Yerges-Armstrong, H.F. Zheng, N. Alonso, J. Eriksson, C.M. Kammerer, S.K. Kaptoge, P.J. Leo, G. Thorleifsson, S.G. Wilson, J.F. Wilson, V. Aalto, M. Alen, A.K. Aragaki, T. Aspelund, J.R. Center, Z. Dailiana, D.J. Duggan, M. Garcia, N. Garcia-Giralt, S. Giroux, G. Hallmans, L.J. Hocking, L.B. Husted, K.A. Jameson, R. Khusainova, G.S. Kim, C. Kooperberg, T. Koromila, M. Kruk, M. Laaksonen, A.Z. Lacroix, S.H. Lee, P.C. Leung, J.R. Lewis, L. Masi, S. Mencej-Bedrac, T.V. Nguyen, X. Nogues, M.S. Patel, J. Prezelj, L.M. Rose, S. Scollen, K. Siggeirsdottir, A.V. Smith, O. Svensson, S. Trompet, O. Trummer, N.M. van Schoor, J. Woo, K. Zhu, S. Balcells, M.L. Brandi, B.M. Buckley, S. Cheng, C. Christiansen, C. Cooper, G. Dedoussis, I. Ford, M. Frost, D. Goltzman, J. González-Macías, M. Kähönen, M. Karlsson, E. Khusnutdinova, J.M. Koh, P. Kollia, B.L. Langdahl, W.D. Leslie, P. Lips, Ö. Ljunggren, R.S. Lorenc, J. Marc, D. Mellström, B. Obermayer-Pietsch, J.M. Olmos, U. Pettersson-Kymmer, D.M. Reid, J.A. Riancho, P.M. Ridker, F. Rousseau, P.E. Slagboom, N.L. Tang, R. Urreizti, W. Van Hul, J. Viikari, M.T. Zarrabeitia, Y.S. Aulchenko, M. Castano-Betancourt, E. Grundberg, L. Herrera, T. Ingvarsson, H. Johannsdottir, T. Kwan, R. Li, R. Luben, C. Medina-Gómez, S.T. Palsson, S. Reppe, J.I. Rotter, G. Sigurdsson, J.B. van Meurs, D. Verlaan, F.M. Williams, A.R. Wood, Y. Zhou, K.M. Gautvik, T. Pastinen, S. Raychaudhuri, J.A. Cauley, D.I. Chasman, G.R. Clark, S.R. Cummings, P. Danoy, E.M. Dennison, R. Eastell, J.A. Eisman, V. Gudnason, A. Hofman, R.D. Jackson, G. Jones, J.W. Jukema, K.T. Khaw, T. Lehtimäki, Y. Liu, M. Lorentzon, E. McCloskey, B.D. Mitchell, K. Nandakumar, G.C. Nicholson, B.A. Oostra, M. Peacock, H.A. Pols, R.L. Prince, O. Raitakari, I.R. Reid, J. Robbins, P.N. Sambrook, P.C. Sham, A.R. Shuldiner, F.A. Tylavsky, N.J. van Duijn CM,Wareham, L.A. Cupples, M.J. Econs, D.M. Evans, T.B. Harris, A.W. Kung, B.M. Psaty, J. Reeve, T.D. Spector, E.A. Streeten, M.C. Zillikens, U. Thorsteinsdottir, C. Ohlsson, D. Karasik, J.B. Richards, M.A. Brown, K. Stefansson, A.G. Uitterlinden, S.H. Ralston, J.P. Ioannidis, D.P. Kiel, F. Rivadeneira, Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat. Genet. 44(5), 491–501 (2012)CrossRef
10.
D.L. Koller, H.F. Zheng, D. Karasik, L. Yerges-Armstrong, C.T. Liu, F. McGuigan, J.P. Kemp, S. Giroux, D. Lai, H.J. Edenberg, M. Peacock, S.A. Czerwinski, A.C. Choh, G. McMahon, B. St Pourcain, N.J. Timpson, D.A. Lawlor, D.M. Evans, B. Towne, J. Blangero, M.A. Carless, C. Kammerer, D. Goltzman, C.S. Kovacs, J.C. Prior, T.D. Spector, F. Rousseau, J.H. Tobias, K. Akesson, M.J. Econs, B.D. Mitchell, J.B. Richards, D.P. Kiel, T. Foroud, Meta-analysis of genome-wide studies identifies WNT16 and ESR1 SNPs associated with bone mineral density in premenopausal women. J. Bone Miner. Res.: Off. J. Am. Soc. Bone Miner. Res. 28(3), 547–558 (2013)CrossRef
11.
U. Styrkarsdottir, G. Thorleifsson, P. Sulem, D.F. Gudbjartsson, A. Sigurdsson, A. Jonasdottir, A. Jonasdottir, A. Oddsson, A. Helgason, O.T. Magnusson, G.B. Walters, M.L. Frigge, H.T. Helgadottir, H. Johannsdottir, K. Bergsteinsdottir, M.H. Ogmundsdottir, J.R. Center, T.V. Nguyen, J.A. Eisman, C. Christiansen, E. Steingrimsson, J.G. Jonasson, L. Tryggvadottir, G.I. Eyjolfsson, A. Theodors, T. Jonsson, T. Ingvarsson, I. Olafsson, T. Rafnar, A. Kong, G. Sigurdsson, G. Masson, U. Thorsteinsdottir, K. Stefansson, Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits. Nature 497(7450), 517–520 (2013)CrossRef
12.
U. Styrkarsdottir, G. Thorleifsson, B. Eiriksdottir, S.A. Gudjonsson, T. Ingvarsson, J.R. Center, T.V. Nguyen, J.A. Eisman, C. Christiansen, U. Thorsteinsdottir, G. Sigurdsson, K. Stefansson, Two rare mutations in the COL1A2 gene associate with low bone mineral density and fractures in Iceland. J. Bone Miner. Res.: Off. J. Am. Soc. Bone Miner. Res. 31(1), 173–179 (2016)CrossRef
13.
L. Zhang, H.J. Choi, K. Estrada, P.J. Leo, J. Li, Y.F. Pei, Y. Zhang, Y. Lin, H. Shen, Y.Z. Liu, Y. Liu, Y. Zhao, J.G. Zhang, Q. Tian, Y.P. Wang, Y. Han, S. Ran, R. Hai, X.Z. Zhu, S. Wu, H. Yan, X. Liu, T.L. Yang, Y. Guo, F. Zhang, Y.F. Guo, Y. Chen, X. Chen, L. Tan, L. Zhang, F.Y. Deng, H. Deng, F. Rivadeneira, E.L. Duncan, J.Y. Lee, B.G. Han, N.H. Cho, G.C. Nicholson, E. McCloskey, R. Eastell, R.L. Prince, J.A. Eisman, G. Jones, I.R. Reid, P.N. Sambrook, E.M. Dennison, P. Danoy, L.M. Yerges-Armstrong, E.A. Streeten, T. Hu, S. Xiang, C.J. Papasian, M.A. Brown, C.S. Shin, A.G. Uitterlinden, H.W. Deng, Multistage genome-wide association meta-analyses identified two new loci for bone mineral density. Hum. Mol. Genet. 23(7), 1923–1933 (2014)CrossRef
14.
C. Medina-Gomez, J.P. Kemp, N.L. Dimou, E. Kreiner, A. Chesi, B.S. Zemel, K. Bønnelykke, C.G. Boer, T.S. Ahluwalia, H. Bisgaard, E. Evangelou, D.H.M. Heppe, L.F. Bonewald, J.P. Gorski, M. Ghanbari, S. Demissie, G. Duque, M.T. Maurano, D.P. Kiel, Y.H. Hsu, C.J.V.D.E. B, C. Ackert-Bicknell, S. Reppe, K.M. Gautvik, T. Raastad, D. Karasik, J. van de Peppel, V.W.V. Jaddoe, A.G. Uitterlinden, J.H. Tobias, S.F.A. Grant, P.G. Bagos, D.M. Evans, F. Rivadeneira, Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. Nat. Commun. 8(1), 121 (2017)CrossRef
15.
N.K. Arden, T.D. Spector, Genetic influences on muscle strength, lean body mass, and bone mineral density: a twin study. J. Bone Miner. Res.: Off. J. Am. Soc. Bone Miner. Res. 12(12), 2076–2081 (1997)CrossRef
16.
N. Mancuso, H. Shi, P. Goddard, G. Kichaev, A. Gusev, B. Pasaniuc, Integrating gene expression with summary association statistics to identify genes associated with 30 complex traits. Am. J. Hum. Genet. 100(3), 473 (2017)CrossRef
17.
D.L. Nicolae, E. Gamazon, W. Zhang, S. Duan, M.E. Dolan, N.J. Cox, Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS. Plos Genet. 6(4), e1000888 (2010)CrossRef
18.
A. Gusev, A. Ko, Integrative approaches for large-scale transcriptome-wide association studies. 48(3), 245–252 (2016)
19.
A. Gusev, N. Mancuso, H. Won, M. Kousi, H.K. Finucane, Y. Reshef, L. Song, A. Safi, S. Mccarroll, B.M. Neale, Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. Nat. Genet. 50(4), 538–548 (2018)CrossRef
20.
S. Thériault, N. Gaudreault, M. Lamontagne, M. Rosa, M. C. Boulanger, D. Messika-Zeitoun, M. A. Clavel, R. Capoulade, F. Dagenais, P. Pibarot, A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis. Nat. Commun. 9(1), (2018)
21.
T. Jiang, Y. Wang, M. Zhu, Y. Wang, M. Huang, G. Jin, X. Guo, J. Sha, J. Dai, Z. Hu, Transcriptome-wide association study revealed two novel genes associated with nonobstructive azoospermia in a Chinese population. Fertil. Steril. 108(6), 1056–1062 (2017)CrossRef
22.
H. Lin, K.L. Lunetta, Q. Zhao, J. Rong, E.J. Benjamin, M.M. Mendelson, R. Joehanes, D. Levy, M.G. Larson, J.M. Murabito, Transcriptome-wide association study of inflammatory biologic age. Aging 9(11), 2288–2301 (2017)CrossRef
23.
A.N. Barbeira, M. Pividori, J. Zheng, H.E. Wheeler, D.L. Nicolae, H.K. Im, Integrating predicted transcriptome from multiple tissues improves association detection. PLoS Genet. 15(1), e1007889 (2019)CrossRef
24.
C.J. Hernandez, A.H. Moeller, The microbiome: A heritable contributor to bone morphology? Semin. Cell Developmental Biol. 123, 82–87 (2022)CrossRef
25.
Pan M. L., L. R. Chen, H. M. Tsao, K. H. Chen, Iron deficiency anemia as a risk factor for osteoporosis in Taiwan: a nationwide population-based study. Nutrients 9(6), (2017)
26.
R.J. Valderrábano, L.Y. Lui, J. Lee, S.R. Cummings, E.S. Orwoll, A.R. Hoffman, J.Y. Wu, Bone density loss is associated with blood cell counts. J. Bone Miner. Res.: Off. J. Am. Soc. Bone Miner. Res. 32(2), 212–220 (2017)CrossRef
27.
Y. Ingenbleek, Plasma transthyretin as a biomarker of sarcopenia in elderly subjects. Nutrients. 11(4), (2019)
28.
K. Kehoe, H. Noels, W. Theelen, E. De Hert, S. Xu, A. Verrijken, T. Arnould, E. Fransen, N. Hermans, A.M. Lambeir, P. Venge, L. Van Gaal, I. De Meester, Prolyl carboxypeptidase activity in the circulation and its correlation with body weight and adipose tissue in lean and obese subjects. PloS One 13(5), e0197603 (2018)CrossRef
29.
Y. Zhou, B. Zhou, L. Pache, M. Chang, A.H. Khodabakhshi, O. Tanaseichuk, C. Benner, S.K. Chanda, Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10(1), 1523 (2019)CrossRef
30.
K. Dessalle, V. Euthine, S. Chanon, J. Delarichaudy, I. Fujii, S. Rome, H. Vidal, G. Nemoz, C. Simon, E. Lefai, SREBP-1 transcription factors regulate skeletal muscle cell size by controlling protein synthesis through myogenic regulatory factors. PloS One 7(11), e50878 (2012)CrossRef
31.
V. Lecomte, E. Meugnier, V. Euthine, C. Durand, D. Freyssenet, G. Nemoz, S. Rome, H. Vidal, E. Lefai, A new role for sterol regulatory element binding protein 1 transcription factors in the regulation of muscle mass and muscle cell differentiation. Mol. Cell. Biol. 30(5), 1182–1198 (2010)CrossRef
32.
C. Shochat, Z. Wang, C. Mo, S. Nelson, R. Donaka, J. Huang, D. Karasik, M. Brotto, Deletion of SREBF1, a functional bone-muscle pleiotropic gene, alters bone density and lipid signaling in zebrafish. Endocrinology. 162(1), (2021)
33.
X.C. Zhang, J. Chen, C.H. Su, H.Y. Yang, M.H. Lee, Roles for CSN5 in control of p53/MDM2 activities. J. Cell. Biochem. 103(4), 1219–1230 (2008)CrossRef
34.
G. Liu, F.X. Claret, F. Zhou, Y. Pan, Jab1/COPS5 as a novel biomarker for diagnosis, prognosis, therapy prediction and therapeutic tools for human cancer. Front. Pharmacol. 9, 135 (2018)CrossRef
35.
R.K. Miller, H. Qadota, T.J. Stark, K.B. Mercer, T.S. Wortham, A. Anyanful, G.M. Benian, CSN-5, a component of the COP9 signalosome complex, regulates the levels of UNC-96 and UNC-98, two components of M-lines in Caenorhabditis elegans muscle. Mol. Biol. Cell 20(15), 3608–3616 (2009)CrossRef
36.
D. Sacks, B. Baxter, B.C.V. Campbell, J.S. Carpenter, C. Cognard, D. Dippel, M. Eesa, U. Fischer, K. Hausegger, J.A. Hirsch, M. Shazam Hussain, O. Jansen, M.V. Jayaraman, A.A. Khalessi, B.W. Kluck, S. Lavine, P.M. Meyers, S. Ramee, D.A. Rüfenacht, C.M. Schirmer, D. Vorwerk, Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke. Int. J. Stroke.: Off. J. Int. Stroke. Soc. 13(6), 612–632 (2018)
37.
W.E. Samsa, M.K. Mamidi, B.S. Hausman, L.A. Bashur, E.M. Greenfield, G. Zhou, The master developmental regulator Jab1/Cops5/Csn5 is essential for proper bone growth and survival in mice. Bone 143, 115733 (2021)CrossRef
38.
J. Kular, J.C. Tickner, N.J. Pavlos, H.M. Viola, T. Abel, B.S. Lim, X. Yang, H. Chen, R. Cook, L.C. Hool, M.H. Zheng, J. Xu, Choline kinase β mutant mice exhibit reduced phosphocholine, elevated osteoclast activity, and low bone mass. J. Biol. Chem. 290(3), 1729–1742 (2015)CrossRef
39.
F. Okamoto, H. Kajiya, K. Toh, S. Uchida, M. Yoshikawa, S. Sasaki, M.A. Kido, T. Tanaka, K. Okabe, Intracellular ClC-3 chloride channels promote bone resorption in vitro through organelle acidification in mouse osteoclasts. Am. J. Physiol. Cell Physiol. 294(3), C693–701 (2008)CrossRef
40.
U. Kornak, D. Kasper, M.R. Bösl, E. Kaiser, M. Schweizer, A. Schulz, W. Friedrich, G. Delling, T.J. Jentsch, Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 104(2), 205–215 (2001)CrossRef
41.
G. Haliloglu, B. Talim, C.G. Sel, H. Topaloglu, Clinical characteristics of megaconial congenital muscular dystrophy due to choline kinase beta gene defects in a series of 15 patients. J. Inherit. Metab. Dis. 38(6), 1099–1108 (2015)CrossRef
42.
J.M. Hock, V. Krishnan, J.E. Onyia, J.P. Bidwell, J. Milas, D. Stanislaus, Osteoblast apoptosis and bone turnover. J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res. 16(6), 975–984 (2001)CrossRef
43.
T. Moriishi, Z. Maruyama, R. Fukuyama, M. Ito, T. Miyazaki, H. Kitaura, H. Ohnishi, T. Furuichi, Y. Kawai, R. Masuyama, H. Komori, K. Takada, H. Kawaguchi, T. Komori, Overexpression of Bcl2 in osteoblasts inhibits osteoblast differentiation and induces osteocyte apoptosis. PloS One 6(11), e27487 (2011)CrossRef
44.
R.S. Weinstein, Glucocorticoid-induced osteonecrosis. Endocrine 41(2), 183–190 (2012)CrossRef
45.
E. Jimi, K. Aoki, H. Saito, F. D’Acquisto, M.J. May, I. Nakamura, T. Sudo, T. Kojima, F. Okamoto, H. Fukushima, K. Okabe, K. Ohya, S. Ghosh, Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nat. Med. 10(6), 617–624 (2004)CrossRef
46.
S. Adhikary, D. Choudhary, N. Ahmad, A. Karvande, A. Kumar, V.T. Banala, P.R. Mishra, R. Trivedi, Dietary flavonoid kaempferol inhibits glucocorticoid-induced bone loss by promoting osteoblast survival. Nutr. (Burbank, Los Angeles Cty., Calif.) 53, 64–76 (2018)CrossRef
47.
R. Khalil, Ubiquitin-proteasome pathway and muscle atrophy. Adv. Exp. Med. Biol. 1088, 235–248 (2018)CrossRef
48.
S.M. Ebert, A. Al-Zougbi, S.C. Bodine, C.M. Adams, Skeletal muscle atrophy: discovery of mechanisms and potential therapies. Physiology (Bethesda. Md) 34(4), 232–239 (2019).
49.
D. Dardevet, D. Rémond, M.A. Peyron, I. Papet, I. Savary-Auzeloux, L. Mosoni, Muscle wasting and resistance of muscle anabolism: the “anabolic threshold concept” for adapted nutritional strategies during sarcopenia. TheScientificWorldJournal 2012, 269531 (2012)CrossRef
50.
A. Adam-Perrot, P. Clifton, F. Brouns, Low-carbohydrate diets: nutritional and physiological aspects. Obes. Rev. 7(1), 49–58 (2006)CrossRef
51.
U. Bradley, M. Spence, C.H. Courtney, M.C. McKinley, C.N. Ennis, D.R. McCance, J. McEneny, P.M. Bell, I.S. Young, S.J. Hunter, Low-fat versus low-carbohydrate weight reduction diets: effects on weight loss, insulin resistance, and cardiovascular risk: a randomized control trial. Diabetes 58(12), 2741–2748 (2009)CrossRef
52.
J. Dresios, P. Panopoulos, C.P. Frantziou, D. Synetos, Yeast ribosomal protein deletion mutants possess altered peptidyltransferase activity and different sensitivity to cycloheximide. Biochemistry 40(27), 8101–8108 (2001)CrossRef
53.
J.M. Liu, S.R. Ellis, Ribosomes and marrow failure: coincidental association or molecular paradigm? Blood 107(12), 4583–4588 (2006)CrossRef
54.
D.S. Oristian, L.G. Sloofman, X. Zhou, L. Wang, M.C. Farach-Carson, C.B. Kirn-Safran, Ribosomal protein L29/HIP deficiency delays osteogenesis and increases fragility of adult bone in mice. J. Orthop. Res. Off. Publ. Orthop. Res. Soc. 27(1), 28–35 (2009)CrossRef
55.
D.C. Jones, M.N. Wein, M. Oukka, J.G. Hofstaetter, M.J. Glimcher, L.H. Glimcher, Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science 312(5777), 1223–1227 (2006)CrossRef
Metadata
Title
Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children
Authors
Jiawen Xu
Jun Ma
Yi Zeng
Haibo Si
Yuangang Wu
Shaoyun Zhang
Bin Shen
Publication date
27-12-2022
Publisher
Springer US
Published in
Endocrine / Issue 2/2023
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-022-03225-2

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