Identification of pleiotropic loci underlying hip bone mineral density and trunk lean mass

Abstract

Bone mineral density (BMD) and lean body mass (LBM) not only have a considerable heritability each, but also are genetically correlated. However, common genetic determinants shared by both traits are largely unknown. In the present study, we performed a bivariate genome-wide association study (GWAS) meta-analysis of hip BMD and trunk lean mass (TLM) in 11,335 subjects from 6 samples, and performed replication in estimated heel BMD and TLM in 215,234 UK Biobank (UKB) participants. We identified 2 loci that nearly attained the genome-wide significance (GWS, p < 5.0 × 10−8) level in the discovery GWAS meta-analysis and that were successfully replicated in the UKB sample: 11p15.2 (lead SNP rs12800228, discovery p = 2.88 × 10−7, replication p = 1.95 × 10−4) and 18q21.32 (rs489693, discovery p = 1.67 × 10−7, replication p = 1.17 × 10−3). The above 2 pleiotropic loci may play a pleiotropic role for hip BMD and TLM development. So our findings provide useful insights that further enhance our understanding of genetic interplay between BMD and LBM.

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Acknowledgements

We appreciate all the volunteers who participated into this study. This analysis of the UK Biobank sample was conducted using the UK Biobank resource under application number 41542. Y.F.P. and L.Z. are partially supported by the funding from national natural science foundation of China (31501026, 31771417 and 31571291), a project funded by the Priority Academic Program Development (PAPD) of Jiangsu higher education institutions. H.W.D. is partially supported by the National Institutes of Health (R01AR059781, P20GM109036, R01MH107354, R01MH104680, R01GM109068, R01AR069055, U19AG055373, R01DK115679), the Edward G. Schlieder Endowment and the Drs. W. C. Tsai and P. T. Kung Professorship in Biostatistics from Tulane University. The numerical calculations in this paper have been done on the supercomputing system of the National Supercomputing Center in Changsha. The funders had no role in study design, data collection and analysis, results interpretation or preparation of the manuscript.

The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. Funding for SHARe Affymetrix genotyping was provided by NHLBI Contract N02-HL-64278. SHARe Illumina genotyping was provided under an agreement between Illumina and Boston University. Funding support for the Framingham Whole Body and Regional Dual X-ray Absorptiometry (DXA) dataset was provided by NIH grants R01 AR/AG 41398. The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap through dbGaP accession phs000342.v14.p10.

The WHI program is funded by the National Heart, Lung, and Blood Institute, National 20 Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. This manuscript was not prepared in collaboration with investigators of the WHI, has not been reviewed and/or approved by the Women’s Health Initiative (WHI), and does not necessarily reflect the opinions of the WHI investigators or the NHLBI. Funding for WHI SHARe genotyping was provided by NHLBI Contract N02-HL-64278. The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap through dbGaP accession phs000200.v10.p3. The authors state that there is no conflict of interest.

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Feng, G., Wei, X., Zhang, H. et al. Identification of pleiotropic loci underlying hip bone mineral density and trunk lean mass. J Hum Genet (2020). https://doi.org/10.1038/s10038-020-00835-4

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