Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med 2010;363(2):166-76.
DOI: 10.1056/NEJMra0905980
Cannon ME, Karen LM. Deciphering the emerging complexities of molecular mechanisms at GWAS loci. Am J Hum Genet 2018;103(5):637-53.
DOI: 10.1016/j.ajhg.2018.10.001
Vissecher PV, Wray N, Zhang Q, Sklar P, McCarthy M, Brown M, et al. 10 Years of GWAS discovery: biology, function, and translation. Am J Hum Genet 2017;101(1):5-22.
DOI: 10.1016/j.ajhg.2017.06.005
Buniello A, MacArthur J, Cerezo M, Harris L, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res 2019;47(D1):D1005-12.
DOI: 10.1093/nar/gky1120
Medina-Gomez C, Kemp J, Estrada K, Eriksson J, Liu J, Reppe S, et al. Meta-analysis of genome-wide scans for total body BMD in children and adults reveals allelic heterogeneity and age-specific effects at the WNT16 locus. PLoS Genet 2012;8(7):e1002718.
DOI: 10.1371/journal.pgen.1002718
Loic Y, Sidorenko J, Kemper K, Zheng Z, Wood A, Weedon M, et al. Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Hum Mol Genet 2018;27(20):3641-9.
DOI: 10.1093/hmg/ddy271
Tam V, Patel N, Turcotte M, Bossé Y, Paré G, Meyre D. Benefits and limitations of genome-wide association studies. Nat Rev Genet 2019;20(8):467-84.
DOI: 10.1038/s41576-019-0127-1
Hirschhorn JN. Genomewide association studies — illuminating biologic pathways. N Engl J Med 2009;360(17):1699-701.
DOI: 10.1056/NEJMp0808934
Schaid DJ, Chen W, Larson NB. From Genome-wide associations to candidate causal variants by statistical fine-mapping. Nat Rev Genet 2018;19(8):491-504.
DOI: 10.1038/s41576-018-0016-z
Broekema RV, Bakker OB, Jonkers IH. A practical view of fine-mapping and gene prioritization in the post-genome-wide association era. Open Biol 2020;10(1):190221.
DOI: 10.1098/rsob.190221
Martínez-Gil N, Roca-Ayats N, Atalay N, Pineda-Moncusí M, Garcia-Giralt N, Van Hul W, et al. Functional assessment of coding and regulatory variants from the DKK1 locus. JBMR plus 2020;4(12):e10423.
DOI: 10.1002/jbm4.10423
Schartl M. Beyond the zebrafish: diverse fish species for modeling human disease. Dis Model Mech 2014;7(2):181-92.
Rao S, Yao Y, Bauer DE. Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation. Genome Med 2021;13(1):41.
DOI: 10.1186/s13073-021-00857-3
Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 2012;44(5):491-501.
DOI: 10.1038/ng.2249
Morris JA, Kemp JA, Youlten SE, Laurent L, Logan JG, Chai RC, et al. An atlas of genetic influences on osteoporosis in humans and mice. Nat Genet 2019;51(2):258-66.
DOI: 10.1038/s41588-018-0302-x
Trajanoska K, Morris JA, Oei L, Zheng H-F, Evans DM, Kiel DP, et al. Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study. BMJ 2018;362:k3225.
DOI: 10.1136/bmj.k3225
García-Ibarbia C, Delgado-Calle J, Casafont I, Velasco J, Arozamena J, Pérez-Núñez M, et al. Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in prevalent skeletal disorders. Gene 2013;532(2):165-72.
DOI: 10.1016/j.gene.2013.09.080
Ohkawara B, Cabrera-Serrano M, Nakata T, Milone M, Asai N, Ito K, et al. LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. Hum Mol Genet 2014;23(7):1856-68.
DOI: 10.1093/hmg/ddt578
Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, et al. New sequence variants associated with bone mineral density. Nat Genet 2009;41(1):15-7.
DOI: 10.1038/ng.284
Rivadeneira F, Styrkársdottir U, Estrada K, Halldórsson BV, Hsu Y-H, Richards JB, et al. Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet 2009;41(11):1199-206.
DOI: 10.1038/ng.446
Guo Y, Tan L-J, Lei S-F, Yang T-L, Chen X-D, Zhang F, et al. Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis. PLoS Genet 2010;6(1):e1000806.
DOI: 10.1371/journal.pgen.1000806
Kung AW, Xiao SM, Cherny S, Li GH, Gao Y, Tso G, et al. Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies. Am J Hum Genet 2010;86(2):229-39.
DOI: 10.1016/j.ajhg.2009.12.014
Hsu YH, Zillikens MC, Wilson SG, Farber CR, Demissie S, Soranzo N, et al. An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility loci for osteoporosis-related traits. PLoS Genet 2010;6(6):e1000977.
DOI: 10.1371/journal.pgen.1000977
Styrkarsdottir U, Thorleifsson G, Sulem P, Gudbjartsson DF, Sigurdsson A, Aslaug J, et al. Nonsense mutation in the LGR4 gene is associated with several human diseases and other traits. Nature 2013;497(7450):517-20.
DOI: 10.1038/nature12124
Zhang L, Choi HJ, Estrada K, Leo PJ, Li J, Pei Y-F, et al. Multistage genome-wide association meta-analyses identified two new loci for bone mineral density. Hum Mol Genet 2014;23(7):1923-33.
DOI: 10.1093/hmg/ddt575
Moayyeri A, Hsu Y-H, Karasik D, Estrada K, Xiao S-M, Nielson C, et al. Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium. Hum Mol Genet 2014;23(11):3054-68.
DOI: 10.1093/hmg/ddt675
Zheng H-F, Forgetta V, Hsu Y-H, Estrada K, Rosello-Diez A, Leo PJ, et al. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 2015;526(7571):112-7.
DOI: 10.1038/nature14878
Styrkarsdottir U, Thorleifsson G, Gudjonsson SA, Sigurdsson A, Center JR, Hun Lee S, et al. Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures. Nat Commun 2016;7:10129.
DOI: 10.1038/ncomms10129
Nielson C, Liu C-T, Smith AV, Ackert-Bicknell C, Reppe S, Jakobsdottir J, et al. Novel genetic variants associated with increased vertebral volumetric BMD, reduced vertebral fracture risk, and increased expression of SLC1A3 and EPHB2. J Bone Miner Res 2016;31(12):2085-97.
DOI: 10.1002/jbmr.2913
Mullin BH, Zhao JH, Brown SJ, Perry J, Luan J, Zheng H-F, et al. Genome-wide association study meta-analysis for quantitative ultrasound parameters of bone identifies five novel loci for broadband ultrasound attenuation. Hum Mol Genet 2017;26(14):2791-802.
DOI: 10.1093/hmg/ddx174
Kemp JP, Morris JA, Medina-Gomez C, Forgetta V, Warrington NM, Youlten SE, et al. Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis. Nat Genet 2017;49(10):1468-75.
DOI: 10.1038/ng.3949
Hollander W, Boer CG, Hart DJ, Yau MS, Ramos Y, Metrustry S, et al. Genome-wide association and functional studies identify a role for matrix Gla protein in osteoarthritis of the hand. Ann Rheum Dis 2017;76(12):2046-53.
DOI: 10.1136/annrheumdis-2017-211214
Medina-Gomez C, Kemp JP, Trajanoska K, Luan J, Chesi A, Ahluwalia TS, et al. Life-course genome-wide association study meta-analysis of total body BMD and assessment of age-specific effects. Am J Hum Genet 2018;102(1):88-102.
DOI: 10.1016/j.ajhg.2017.12.005
Pei Y-F, Hu W-Z, Yan M-W, Li C-W, Liu L, Yang X-L, et al. Joint study of two genome-wide association meta-analyses identified 20p12.1 and 20q13.33 for bone mineral density. Bone 2018;110:378-85.
Alonso N, Estrada K, Albagha OME, Herrera L, Reppe S, Olstad OK, et al. Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density. Ann Rheum Dis 2018;77(3):378-85.
DOI: 10.1136/annrheumdis-2017-212469
Kim SK. Identification of 613 new loci associated with heel bone mineral density and a polygenic risk score for bone mineral density, osteoporosis and fracture. PloS One 2018;13(7):e0200785.
DOI: 10.1371/journal.pone.0200785
Baird DA, Evans DS, Kamanu FK, Gregory JS, Saunders FR, Giuraniuc CV, et al. Identification of novel loci associated with hip shape: a meta-analysis of genome wide association studies. J Bone Miner Res 2019;34(2):241-51.
DOI: 10.1002/jbmr.3605
Hsu Y-H, Estrada K, Evangelou E, Ackert-Bicknell C, Akesson K, Beck T, et al. Meta-analysis of genomewide association studies reveals genetic variants for hip bone geometry. J Bone Miner Re. 2019;34(7):1284-96.
DOI: 10.1002/jbmr.3698
Pei YF, Liu L, Liu TL, Yang XL, Zhang H, Wei XT, et al. Joint association analysis identified 18 new loci for bone mineral density. J Bone Miner Re. 2019;34(6):1086-94.
DOI: 10.1002/jbmr.3681
Styrkarsdottir U, Stefansson OA, Gunnarsdottir K, Thorleifsson G, Lund SH, Stefansdottir L, et al. GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures. Nat Commun 2019;10(1):2054.
DOI: 10.1038/s41467-019-09860-0
Zheng J, Maerz W, Gergei I, Kleber M, Drechsler C, Wanner C, et al. Mendelian randomization analysis reveals a causal influence of circulating sclerostin levels on bone mineral density and fractures. J Bone Miner Res 2019;34(10):1824-36.
DOI: 10.1002/jbmr.3803
Feng GJ, Wei XT, Zhang H, Yang XL, Shen H, Tian Q, et al. Identification of pleiotropic loci underlying hip bone mineral density and trunk lean mass. J Hum Genet 2020;66(3):251-60.
DOI: 10.1038/s10038-020-00835-4
Zhang YX, Zhang SS, Ran S, Liu Y, Zhang H, Yang XL, et al. Three pleiotropic loci associated with bone mineral density and lean body mass. Mol Genet Genomics 2020;296(1):55-65.
DOI: 10.1007/s00438-020-01724-3
Surakka I, Fritsche LG, Zhou W, Backman J, Kosmicki JA, Lu H, et al. MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk. Nat Commun 2020;11(1):4093.
DOI: 10.1038/s41467-020-17315-0
Greenbaum J, Su KJ, Zhang X, Liu Y, Liu A, Zhao LJ, et al. A multiethnic whole genome sequencing study to identify novel loci for bone mineral density. Hum Mol Genet 2022;31(7):1067-81.
DOI: 10.1093/hmg/ddab305
Leupin O, Piters E, Halleux C, Hu S, Kramer I, Morvan F, et al. Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem 2011;286(22):19489-500.
DOI: 10.1074/jbc.M110.190330
Choi HY, Dieckmann M, Herz J, Niemeier A. Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo. PloS One 2009;4(11):e7930.
DOI: 10.1371/journal.pone.0007930
Chang M-K, Kramer I, Huber T, Kinzel B, Guth-Gundel S, Leupin O, et al. Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels. Proc Natl Acad Sci USA 2014;111(48):E5187-195.
DOI: 10.1073/pnas.1413828111
Wang R, Zhao P, Kong N, Lu R, Pei Y, Huang C, et al. Genome-wide identification and characterization of the potato bHLH transcription factor family. Genes 2018;22;9(1):54.
DOI: 10.3390/genes9010054
Velázquez-Cruz R, Jiménez-Ortega RF, Parra-Torres AY, Castillejos-López M, Patiño N, Quiterio M, et al. Analysis of association of MEF2C, SOST and JAG1 genes with bone mineral density in Mexican-Mestizo postmenopausal women. BMC Musculoskelet Disord 2014;15:400.
DOI: 10.1186/1471-2474-15-400
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 2016;375(16):1532-43.
DOI: 10.1056/NEJMoa1607948
McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 2014;370(5):412-20.
DOI: 10.1056/NEJMoa1305224
Recker RR, Benson CT, Matsumoto T, Bolognese MA, Robins DA, Alam J, et al. A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density. J Bone Miner Res 2015;30(2):216-24.
DOI: 10.1002/jbmr.2351
Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet 2017;390(10102):1585-94.
DOI: 10.1016/S0140-6736(17)31613-6
Glorieux FH, Devogelaer JP, Durigova M, Goemaere S, Hemsley S, Jakob F, et al. BPS804 anti-sclerostin antibody in adults with moderate osteogenesis imperfecta: results of a randomized phase 2a trial. J Bone Miner Res 2017;32(7):1496-504.
DOI: 10.1002/jbmr.3143
Lewiecki M, Blicharski T, Goemaere S, Lippuner K, Meisner PD, Miller PD, et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab 2018;103(9):3183-93.
DOI: 10.1210/jc.2017-02163
Martínez-Gil N, Ugartondo N, Grinberg D, Balcells S. Wnt pathway extracellular components and their essential roles in bone homeostasis. Genes (Basel) 2022;13(1):138.
DOI: 10.3390/genes13010138
Balemans W, Patel N, Ebeling M, Van Hul E, Wuyts W, Lacza C, et al. Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 2002;39(2):91-7.
DOI: 10.1136/jmg.39.2.91
Collette NM, Genetos DC, Economides AN, Xie L, Shahnazari M, Yao W, et al. Targeted deletion of Sost distal enhancer increases bone formation and bone mass. Proc Natl Acad Sci USA 2012;109(35):14092-7.
DOI: 10.1073/pnas.1207188109
Martínez-Gil N, Roca-Ayats N, Cozar M, Garcia-Giralt N, Ovejero D, Nogués X, et al. Genetics and genomics of SOST: functional analysis of variants and genomic regulation in osteoblasts. Int J Mol Sci 2021;22(2):489.
DOI: 10.3390/ijms22020489
Loots G, Kneissel M, Keller H, Baptist M, Chang J, Collette NM, et al. Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res 2005;15(7):928-35.
DOI: 10.1101/gr.3437105
Kramer I, Baertschi S, Halleux C, Keller H, Kneissel M. Mef2c deletion in osteocytes results in increased bone mass. J Bone Miner Res 2012;27(2):360-73.
DOI: 10.1002/jbmr.1492
Duncan E, Danoy P, Kemp JP, Leo PJ, McCloskey E, Nicholson GC, et al. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet 2011;7(4):e1001372. Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk
DOI: 10.1371/journal.pgen.1001372
Pei YF, Hu WZ, Hai R, Wang XY, Ran S, Lin Y, et al. Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density. Bone 2016;91:1-10.
DOI: 10.1016/j.bone.2016.07.004
Zheng HF, Duncan EL, Yerges-Armstrong LM, Eriksson J, Bergström U, Leo PJ, et al. Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm. J Med Genet 2013;50(7):473-8.
DOI: 10.1136/jmedgenet-2012-101287
Gregson CL, Newell F, Leo PJ, Clark GR, Paternoster L, Marshall M, et al. Genome-wide association study of extreme high bone mass: contribution of common genetic variation to extreme BMD phenotypes and potential novel BMD-associated genes. Bone 2018;114:62-71.
DOI: 10.1016/j.bone.2018.06.001
Baertschi S, Baur N, Lueders-Lefevre V, Voshol J, Keller H. Class I and IIa histone deacetylases have opposite effects on sclerostin gene regulation. J Biol Chem 2014;289(36):24995-5009.
DOI: 10.1074/jbc.M114.564997
Kobayashi Y, Uehara S, Koide M. Regulations of osteoclast formation and function by Wnt signals. Clin Calcium 2019;29(3):309-15.
Wein M, Fretwurst T, Nahles S, Duttenhoefer F, Tomakidi P, Steinberg T, et al. Pilot investigation of the molecular discrimination of human osteoblasts from different bone entities. J Craniomaxillofac Surg 2015;43(8):1487-93.
DOI: 10.1016/j.jcms.2015.07.030
Kichaev G, Bhatia G, Loh PR, Gazal S, Burch K, Freund MK, et al. Leveraging polygenic functional enrichment to improve GWAS power. Am J Hum Genet 2019;104(1):65-75.
DOI: 10.1016/j.ajhg.2018.11.008
Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci 2003;116(13):2627-34.
DOI: 10.1242/jcs.00623
Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 1998;391(6665):357-62.
DOI: 10.1038/34848
Ai M, Heeger S, Bartels CF, Schelling DK, Osteoporosis-Pseudoglioma Collaborative Group. Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet 2005;77(5):741-53.
DOI: 10.1086/497706
Balemans W, Devogelaer JP, Cleiren E, Piters E, Caussin E, Van Hul W. Novel LRP5 missense mutation in a patient with a high bone mass phenotype results in decreased DKK1-mediated inhibition of Wnt signaling. J Bone Miner Res 2007;22(5):708-16.
DOI: 10.1359/jbmr.070211
Martínez-Gil N, Roca-Ayats N, Monistrol-Mula A, García-Giralt N, Díez-Pérez A, Nogués X, et al. Common and rare variants of WNT16, DKK1 and SOST and their relationship with bone mineral density. Sci Rep 2018;8(1):10951.
DOI: 10.1038/s41598-018-29242-8
Korvala J, Löija M, Mäkitie O, Sochett E, Jüppner H, Schnabel D, et al. Rare variations in WNT3A and DKK1 may predispose carriers to primary osteoporosis. Eur J Med Genet 2012;55(10):515-9.
DOI: 10.1016/j.ejmg.2012.06.011
van de Putte R, Wijers CH, de Blaauw I, Feitz WF, Marcelis CL, Hakobjan M, et al. Sequencing of the DKK1 gene in patients with anorectal malformations and hypospadias. Eur J Pediatr 2015;174(5):583-7.
DOI: 10.1007/s00431-014-2436-x
Ntini E, Louloupi A, Liz J, Muino JM, Marsico A, Vang-Ørom UA. Long ncRNA A-ROD activates its target gene DKK1 at its release from chromatin. Nat Commun 2018;9(1):1636.
DOI: 10.1038/s41467-018-04100-3
Zheng H-F, Tobias JH, Duncan E, Evans DM, Eriksson J, Paternoster L, et al. WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk. PLoS Genet 2012;8(7):e1002745.
DOI: 10.1371/journal.pgen.1002745
Movérare-Skrtic S, Henning P, Liu X, Nagano K, Saito H, Börjesson AE, et al. Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures. Nat Med 2014;20(11):1279-88.
DOI: 10.1038/nm.3654
Nabbi A, Almami A, Thakur S, Suzuki K, Boland D, Bismar TA, et al. ING3 protein expression profiling in normal human tissues suggest its role in cellular growth and self-renewal. Eur J Cell Biol 2015;94(5):214-22.
DOI: 10.1016/j.ejcb.2015.03.002
Chesi A, Wagley Y, Johnson ME, Manduchi E, Su Ch, Lu S, et al. Genome-scale capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density. Nat Commun 2019;10(1):1260.
DOI: 10.1038/s41467-019-09302-x
Maynard RD, Godfrey DA, Medina-Gomez C, Ackert-Bicknell CL. Characterization of expression and alternative splicing of the gene cadherin-like and PC esterase domain containing 1 (Cped1). Gene 2018;674:127-33.
DOI: 10.1016/j.gene.2018.06.060
Määttä JA, Bendre A, Laanti M, Büki KG,Rantakari P, Tervola P, et al. Fam3c modulates osteogenic cell differentiation and affects bone volume and cortical bone mineral density. Bonekey Rep 2016;5:787.
DOI: 10.1038/bonekey.2016.14
Bendre A, Büki KG, Määttä JA. Fam3c modulates osteogenic differentiation by down-regulating Runx2. Differentiation 2017;93:50-7.
DOI: 10.1016/j.diff.2016.11.005
Martínez-Gil N, Patiño J, Ugartondo N, Grinberg D, Balcells S. WNT16 rs2908004 missense variant acts as eQTL of FAM3C in human primary osteoblasts. Rev Osteoporos Metab Miner 2021;13(4):117-21.
DOI: 10.4321/S1889-836X2021000400003
Martínez-Gil N, Roca-Ayats N, Herrera C, Gritti N, Ugartondo N, Garcia-Giralt N, et al. Functional evidence of bone regulation of WNT16 through upstream enhancers within CPED1. J Bone Miner Res 2020;35:179.
Español
English
Número de descargas:
39585
Número de visitas:
2961
Citas:
0
