Bivariate genome-wide association meta-analysis of paediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus
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Published version
Author(s)
Type
Journal Article
Abstract
Bone mineral density (BMD) 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 BMD (TBLH-BMD) 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 BMD loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3 and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects on 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 BMD and lean mass.
Date Issued
2017-07-25
Date Acceptance
2017-06-01
Citation
Nature Communications, 2017, 8
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
8
Copyright Statement
© The Author(s) 2017. Open Access. This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit
http://creativecommons.org/
licenses/by/4.0/
Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit
http://creativecommons.org/
licenses/by/4.0/
Subjects
MD Multidisciplinary
Publication Status
Published
Article Number
121