Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
- Medina-Gomez, M.C. (Carolina)
- Kemp, J.P. (John)
- Dimou, N.L. (Niki L.)
- Kreiner, E. (Eskil)
- Chesi, A. (Alessandra)
- Zemel, B.S. (Babette S.)
- Bønnelykke, K. (Klaus)
- Boer, C.G. (Cindy G.)
- Ahluwalia, T.S. (Tarunveer Singh)
- Bisgaard, H. (Hans)
- Evangelou, E. (Evangelos)
- Heppe, D.H.M. (Denise)
- Bonewald, L.F. (Lynda F.)
- Gorski, J.P. (Jeffrey P.)
- Ghanbari, M. (Mohsen)
- Demissie, S. (Serkalem)
- Duque, G. (Gustavo)
- Maurano, M.T. (Matthew T.)
- Kiel, D.P. (Douglas P.)
- Hsu, Y.-H. (Yi-Hsiang)
- Eerden, B.C.J. (Bram) van der
- Ackert-Bicknell, C. (Cheryl)
- Reppe, S. (Sjur)
- Gautvik, K.M. (Kaare)
- Raastad, T. (Truls)
- Karasik, D. (David)
- Peppel, J. (Jeroen) van de
- Jaddoe, V.W.V. (Vincent)
- Uitterlinden, A.G. (André)
- Tobias, J.H. (Jon)
- Grant, S.F.A. (Struan)
- Bagos, P.G. (Pantelis G.)
- Evans, D.M. (David)
- Rivadeneira Ramirez, F. (Fernando)
DOIAbstract
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% for TBLH-BMD, and 39% for TB-LM, with a shared genetic component of 43%. 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 a...
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