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20.04.2020 | Original Article

Pleiotropic loci underlying bone mineral density and bone size identified by a bivariate genome-wide association analysis

verfasst von: H. Zhang, L. Liu, J.-J. Ni, X.-T. Wei, G.-J. Feng, X.-L. Yang, Q. Xu, Z.-J. Zhang, R. Hai, Q. Tian, H. Shen, H.-W. Deng, Y.-F. Pei, L. Zhang

Erschienen in: Osteoporosis International | Ausgabe 9/2020

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Abstract

Summary

Aiming to identify pleiotropic genomic loci for bone mineral density and bone size, we performed a bivariate GWAS in five discovery samples and replicated in two large-scale samples. We identified 2 novel loci at 2q37.1 and 6q26. Our findings provide insight into common genetic architecture underlying both traits.

Introduction

Bone mineral density (BMD) and bone size (BS) are two important factors that contribute to the development of osteoporosis and osteoporotic fracture. Both BMD and BS are highly heritable and they are genetically correlated. In this study, we aim to identify pleiotropic loci associated with BMD and BS.

Methods

We conducted a bivariate genome-wide association (GWA) analysis of hip BMD and hip BS in 6180 participants from 5 samples, followed by in silico replication in the UK Biobank study of BMD (N = 426,824) and the deCODE study of BS (N = 28,954), respectively.

Results

SNPs from 2 genomic loci were significant at the genome-wide significance (GWS) level (p lt; 5 × 10⁻⁸) in the discovery samples and were successfully replicated in the replication samples (2q37.1, lead SNP rs7575512, discovery p = 1.49 × 10⁻¹⁰, replication p = 0.05; 6q26, lead SNP rs1040724, discovery p = 1.95 × 10⁻⁸, replication p = 0.03). Functional annotations suggested functional relevance of the identified variants to bone development.

Conclusion

Our findings provide insight into the common genetic architecture underlying BMD and BS, and enhance our understanding of the potential mechanism of osteoporosis fracture.

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Titel: Pleiotropic loci underlying bone mineral density and bone size identified by a bivariate genome-wide association analysis
verfasst von: H. Zhang
L. Liu
J.-J. Ni
X.-T. Wei
G.-J. Feng
X.-L. Yang
Q. Xu
Z.-J. Zhang
R. Hai
Q. Tian
H. Shen
H.-W. Deng
Y.-F. Pei
L. Zhang
Publikationsdatum: 20.04.2020
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 9/2020
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-020-05389-x

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Pleiotropic loci underlying bone mineral density and bone size identified by a bivariate genome-wide association analysis

Abstract

Summary

Introduction

Methods

Results

Conclusion

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