Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-017-00108-3
Keywords
-
Categories
Funding
- UK Medical Research Council
- Wellcome Trust [102215/2/13/2, WT083431MA]
- University of Bristol
- Medical Research Council [MC_UU_12013/4]
- Australian Research Council [FT130101709]
- European Commission [HEALTH-F2-2008-201865-GEFOS]
- Erasmus Medical Center, Rotterdam
- Erasmus University Rotterdam
- Netherlands Organization for Health Research and Development (ZonMw)
- Netherlands Organisation for Scientific Research (NWO)
- Ministry of Health, Welfare and Sport
- Netherlands Organization for Health Research and Development [ZonMw 907.00303, ZonMw 916.10159, ZonMw VIDI 016.136.361, ZonMw VIDI 016.136.367]
- National Institute of Child Health and Human Development (NICHD) [NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331, NO1-HD-1-3332, NO1-HD-1-3333, R01 HD058886]
- Clinical and Translational Research Center [5-MO1-RR-000240, UL1 RR-026314]
- NIH (the American Recovery and Reinvestment Act, ARRA) [5RC2HL102419]
- National institute on Arthritis, Musculoskeletal and Skin Diseases [R01 AR41398]
- Lundbeck Foundation [R163-2013-16235] Funding Source: researchfish
- Medical Research Council [MC_PC_15018, MC_UU_12013/4, G9815508] Funding Source: researchfish
- Steno Diabetes Center Copenhagen (SDCC) [SDCC 3.A Complications] Funding Source: researchfish
- Australian Research Council [FT130101709] Funding Source: Australian Research Council
- MRC [MC_UU_12013/4] Funding Source: UKRI
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available