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

Medina-Gomez, Carolina, Kemp, John P., Dimou, Niki L., Kreiner, Eskil, Chesi, Alessandra, Zemel, Babette S., Bonnelykke, Klaus, Boer, Cindy G., Ahluwalia, Tarunveer S., Bisgaard, Hans, Evangelou, Evangelos, Heppe, Denise H. M., Bonewald, Lynda F., Gorski, Jeffrey P., Ghanbari, Mohsen, Demissie, Serkalem, Duque, Gustavo, Maurano, Matthew T., Kiel, Douglas P., Hsu, Yi-Hsiang, Van Der Eerden, Bram C. J., Ackert-Bicknell, Cheryl, Reppe, Sjur, Gautvik, Kaare M., Raastad, Truls, Karasik, David, Van De Peppel, Jeroen, Jaddoe, Vincent W. V., Uitterlinden, André G., Tobias, Jonathan H., Grant, Struan F.A., Bagos, Pantelis G., Evans, David M. and Rivadeneira, Fernando (2017) Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. Nature Communications, 8 1: . doi:10.1038/s41467-017-00108-3


Author Medina-Gomez, Carolina
Kemp, John P.
Dimou, Niki L.
Kreiner, Eskil
Chesi, Alessandra
Zemel, Babette S.
Bonnelykke, Klaus
Boer, Cindy G.
Ahluwalia, Tarunveer S.
Bisgaard, Hans
Evangelou, Evangelos
Heppe, Denise H. M.
Bonewald, Lynda F.
Gorski, Jeffrey P.
Ghanbari, Mohsen
Demissie, Serkalem
Duque, Gustavo
Maurano, Matthew T.
Kiel, Douglas P.
Hsu, Yi-Hsiang
Van Der Eerden, Bram C. J.
Ackert-Bicknell, Cheryl
Reppe, Sjur
Gautvik, Kaare M.
Raastad, Truls
Karasik, David
Van De Peppel, Jeroen
Jaddoe, Vincent W. V.
Uitterlinden, André G.
Tobias, Jonathan H.
Grant, Struan F.A.
Bagos, Pantelis G.
Evans, David M.
Rivadeneira, Fernando
Title Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
Formatted title
Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
Journal name Nature Communications   Check publisher's open access policy
ISSN 2041-1723
Publication date 2017-06-25
Sub-type Article (original research)
DOI 10.1038/s41467-017-00108-3
Open Access Status DOI
Volume 8
Issue 1
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1600 Chemistry
1300 Biochemistry, Genetics and Molecular Biology
3100 Physics and Astronomy
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.
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Q-Index Status Provisional Code
Institutional Status UQ

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Sub-type: Article (original research)
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