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Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

dc.creatorMedina-Gomez C., Kemp J.P., Dimou N.L., Kreiner E., Chesi A., Zemel B.S., Bønnelykke K., Boer C.G., Ahluwalia T.S., Bisgaard H., Evangelou E., Heppe D.H.M., Bonewald L.F., Gorski J.P., Ghanbari M., Demissie S., Duque G., Maurano M.T., Kiel D.P., Hsu Y.-H., Van Der Eerden B.C.J., Ackert-Bicknell C., Reppe S., Gautvik K.M., Raastad T., Karasik D., Van De Peppel J., Jaddoe V.W.V., Uitterlinden A.G., Tobias J.H., Grant S.F.A., Bagos P.G., Evans D.M., Rivadeneira F.en
dc.date.accessioned2023-01-31T08:58:22Z
dc.date.available2023-01-31T08:58:22Z
dc.date.issued2017
dc.identifier10.1038/s41467-017-00108-3
dc.identifier.issn20411723
dc.identifier.urihttp://hdl.handle.net/11615/76463
dc.description.abstractBone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass. © 2017 The Author(s).en
dc.language.isoenen
dc.sourceNature Communicationsen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85026221320&doi=10.1038%2fs41467-017-00108-3&partnerID=40&md5=d76bb5d9bd60464b70edc84aa62064cb
dc.subjectlow density lipoprotein receptor related protein 5en
dc.subjectmatrix extracellular phosphoglycoproteinen
dc.subjectosteoclast differentiation factoren
dc.subjectWnt4 proteinen
dc.subjectcarrier proteinen
dc.subjectSREBF1 protein, humanen
dc.subjectsterol regulatory element binding protein 1en
dc.subjectTOM1L2 protein, humanen
dc.subjectbiochemical compositionen
dc.subjectboneen
dc.subjectcells and cell componentsen
dc.subjectgene expressionen
dc.subjectgenetic variationen
dc.subjectgenomeen
dc.subjectheritabilityen
dc.subjectmeta-analysisen
dc.subjectmuscleen
dc.subjectpleiotropyen
dc.subjectpolymorphismen
dc.subjectskeletonen
dc.subjectadulten
dc.subjectArticleen
dc.subjectbone densityen
dc.subjectcell differentiationen
dc.subjectchilden
dc.subjectCPED1 geneen
dc.subjectfemaleen
dc.subjectfollow upen
dc.subjectGALNT3 geneen
dc.subjectgeneen
dc.subjectgene locusen
dc.subjectgenetic associationen
dc.subjectgenetic traiten
dc.subjectgenetic variabilityen
dc.subjectgenome-wide association studyen
dc.subjectheritabilityen
dc.subjecthumanen
dc.subjecthuman cellen
dc.subjecthuman tissueen
dc.subjectlean body weighten
dc.subjectmajor clinical studyen
dc.subjectmaleen
dc.subjectmouseen
dc.subjectmuscle developmenten
dc.subjectmuscle tissueen
dc.subjectmusculoskeletal systemen
dc.subjectmyoblasten
dc.subjectnonhumanen
dc.subjectosteoblasten
dc.subjectpediatricsen
dc.subjectpleiotropyen
dc.subjectPPP6R3 geneen
dc.subjectRIN3 geneen
dc.subjectsingle nucleotide polymorphismen
dc.subjectSREBF1 geneen
dc.subjectTOM1L2 geneen
dc.subjectWNT16 geneen
dc.subjectbody weighten
dc.subjectbone densityen
dc.subjectgene expressionen
dc.subjectgeneticsen
dc.subjectgenome-wide association studyen
dc.subjectmeta analysis (topic)en
dc.subjectmultivariate analysisen
dc.subjectmusculoskeletal developmenten
dc.subjectproceduresen
dc.subjectquantitative trait locusen
dc.subjectMurinaeen
dc.subjectBody Weighten
dc.subjectBone Densityen
dc.subjectCarrier Proteinsen
dc.subjectChilden
dc.subjectFemaleen
dc.subjectGene Expressionen
dc.subjectGenetic Pleiotropyen
dc.subjectGenome-Wide Association Studyen
dc.subjectHumansen
dc.subjectMaleen
dc.subjectMeta-Analysis as Topicen
dc.subjectMultivariate Analysisen
dc.subjectMusculoskeletal Developmenten
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectQuantitative Trait Locien
dc.subjectSterol Regulatory Element Binding Protein 1en
dc.subjectNature Publishing Groupen
dc.titleBivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locusen
dc.typejournalArticleen


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