Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
| Autor: | Douglas P. Kiel, Mohsen Ghanbari, Evangelos Evangelou, Alessandra Chesi, John P. Kemp, Yi-Hsiang Hsu, Denise H. M. Heppe, Jeroen van de Peppel, Struan F.A. Grant, Fernando Rivadeneira, Cindy G. Boer, Sjur Reppe, André G. Uitterlinden, David M. Evans, Hans Bisgaard, Kaare M. Gautvik, Bram C. J. van der Eerden, Matthew T. Maurano, Lynda F. Bonewald, Pantelis G. Bagos, Gustavo Duque, Jeffrey P. Gorski, Niki Dimou, Serkalem Demissie, Vincent W. V. Jaddoe, Cheryl L. Ackert-Bicknell, Jonathan H Tobias, Eskil Kreiner, Carolina Medina-Gomez, Klaus Bønnelykke, Babette S. Zemel, Truls Raastad, David Karasik, Tarunveer S. Ahluwalia |
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| Přispěvatelé: | Internal Medicine, Erasmus MC other, Pediatrics |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Male Carrier Proteins/genetics Bone density Science Quantitative Trait Loci General Physics and Astronomy Gene Expression 030209 endocrinology & metabolism Genome-wide association study Locus (genetics) Biology Quantitative trait locus Polymorphism Single Nucleotide Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Meta-Analysis as Topic Bone Density Sterol Regulatory Element Binding Protein 1/genetics MD Multidisciplinary SNP Humans Child Bone mineral Genetics Multidisciplinary Musculoskeletal Development Body Weight nutritional and metabolic diseases Genetic Pleiotropy General Chemistry Heritability 030104 developmental biology genome-wide association studies Multivariate Analysis gene expression Lean body mass Genome-Wide Association Study/methods Female Musculoskeletal Development/genetics Carrier Proteins Sterol Regulatory Element Binding Protein 1 Quantitative Trait Loci/genetics Genome-Wide Association Study |
| Zdroj: | 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, C J van der Eerden, B, 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 2017, ' Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus ', Nature Communications, vol. 8, 121 . https://doi.org/10.1038/s41467-017-00108-3 Nature Communications Nature Communications, 8(1):121. Nature Publishing Group Nature Communications, Vol 8, Iss 1, Pp 1-11 (2017) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-017-00108-3 |
| Popis: | 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. Author summary Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits. |
| Databáze: | OpenAIRE |
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