Mostrar el registro sencillo del ítem
Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
dc.creator | Medina-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.accessioned | 2023-01-31T08:58:22Z | |
dc.date.available | 2023-01-31T08:58:22Z | |
dc.date.issued | 2017 | |
dc.identifier | 10.1038/s41467-017-00108-3 | |
dc.identifier.issn | 20411723 | |
dc.identifier.uri | http://hdl.handle.net/11615/76463 | |
dc.description.abstract | Bone 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.iso | en | en |
dc.source | Nature Communications | en |
dc.source.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85026221320&doi=10.1038%2fs41467-017-00108-3&partnerID=40&md5=d76bb5d9bd60464b70edc84aa62064cb | |
dc.subject | low density lipoprotein receptor related protein 5 | en |
dc.subject | matrix extracellular phosphoglycoprotein | en |
dc.subject | osteoclast differentiation factor | en |
dc.subject | Wnt4 protein | en |
dc.subject | carrier protein | en |
dc.subject | SREBF1 protein, human | en |
dc.subject | sterol regulatory element binding protein 1 | en |
dc.subject | TOM1L2 protein, human | en |
dc.subject | biochemical composition | en |
dc.subject | bone | en |
dc.subject | cells and cell components | en |
dc.subject | gene expression | en |
dc.subject | genetic variation | en |
dc.subject | genome | en |
dc.subject | heritability | en |
dc.subject | meta-analysis | en |
dc.subject | muscle | en |
dc.subject | pleiotropy | en |
dc.subject | polymorphism | en |
dc.subject | skeleton | en |
dc.subject | adult | en |
dc.subject | Article | en |
dc.subject | bone density | en |
dc.subject | cell differentiation | en |
dc.subject | child | en |
dc.subject | CPED1 gene | en |
dc.subject | female | en |
dc.subject | follow up | en |
dc.subject | GALNT3 gene | en |
dc.subject | gene | en |
dc.subject | gene locus | en |
dc.subject | genetic association | en |
dc.subject | genetic trait | en |
dc.subject | genetic variability | en |
dc.subject | genome-wide association study | en |
dc.subject | heritability | en |
dc.subject | human | en |
dc.subject | human cell | en |
dc.subject | human tissue | en |
dc.subject | lean body weight | en |
dc.subject | major clinical study | en |
dc.subject | male | en |
dc.subject | mouse | en |
dc.subject | muscle development | en |
dc.subject | muscle tissue | en |
dc.subject | musculoskeletal system | en |
dc.subject | myoblast | en |
dc.subject | nonhuman | en |
dc.subject | osteoblast | en |
dc.subject | pediatrics | en |
dc.subject | pleiotropy | en |
dc.subject | PPP6R3 gene | en |
dc.subject | RIN3 gene | en |
dc.subject | single nucleotide polymorphism | en |
dc.subject | SREBF1 gene | en |
dc.subject | TOM1L2 gene | en |
dc.subject | WNT16 gene | en |
dc.subject | body weight | en |
dc.subject | bone density | en |
dc.subject | gene expression | en |
dc.subject | genetics | en |
dc.subject | genome-wide association study | en |
dc.subject | meta analysis (topic) | en |
dc.subject | multivariate analysis | en |
dc.subject | musculoskeletal development | en |
dc.subject | procedures | en |
dc.subject | quantitative trait locus | en |
dc.subject | Murinae | en |
dc.subject | Body Weight | en |
dc.subject | Bone Density | en |
dc.subject | Carrier Proteins | en |
dc.subject | Child | en |
dc.subject | Female | en |
dc.subject | Gene Expression | en |
dc.subject | Genetic Pleiotropy | en |
dc.subject | Genome-Wide Association Study | en |
dc.subject | Humans | en |
dc.subject | Male | en |
dc.subject | Meta-Analysis as Topic | en |
dc.subject | Multivariate Analysis | en |
dc.subject | Musculoskeletal Development | en |
dc.subject | Polymorphism, Single Nucleotide | en |
dc.subject | Quantitative Trait Loci | en |
dc.subject | Sterol Regulatory Element Binding Protein 1 | en |
dc.subject | Nature Publishing Group | en |
dc.title | Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus | en |
dc.type | journalArticle | en |
Ficheros en el ítem
Ficheros | Tamaño | Formato | Ver |
---|---|---|---|
No hay ficheros asociados a este ítem. |