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Published in: Calcified Tissue International 5/2017

01-11-2017 | Original Research

Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer

Authors: Cheng Peng, Hui-Ling Lou, Feng Liu, Jie Shen, Xu Lin, Chun-Ping Zeng, Ji-Rong Long, Kuan-Jui Su, Lan Zhang, Jonathan Greenbaum, Wei-Feng Deng, Yu-Mei Li, Hong-Wen Deng

Published in: Calcified Tissue International | Issue 5/2017

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Abstract

Epidemiological and clinical evidences have shown that bone mineral density (BMD) has a close relationship with breast cancer (BC). They might potentially have a shared genetic basis. By incorporating information about these pleiotropic effects, we may be able to explore more of the traits’ total heritability. We applied a recently developed conditional false discovery rate (cFDR) method to the summary statistics from two independent GWASs to identify the potential pleiotropic genetic variants for BMD and BC. By jointly analyzing two large independent GWASs of BMD and BC, we found strong pleiotropic enrichment between them and identified 102 single-nucleotide polymorphisms (SNPs) in BMD and 192 SNPs in BC with cFDR < 0.05, including 230 SNPs that might have been overlooked by the standard GWAS analysis. cFDR-significant genes were enriched in GO terms and KEGG pathways which were crucial to bone metabolism and/or BC pathology (adjP < 0.05). Some cFDR-significant genes were partially validated in the gene expressional validation assay. Strong interactions were found between proteins produced by cFDR-significant genes in the context of biological mechanism of bone metabolism and/or BC etiology. Totally, we identified 7 pleiotropic SNPs that were associated with both BMD and BC (conjunction cFDR < 0.05); CCDC170, ESR1, RANKL, CPED1, and MEOX1 might play important roles in the pleiotropy of BMD and BC. Our study highlighted the significant pleiotropy between BMD and BC and shed novel insight into trait-specific as well as the potentially shared genetic architecture for both BMD and BC.
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Metadata
Title
Enhanced Identification of Potential Pleiotropic Genetic Variants for Bone Mineral Density and Breast Cancer
Authors
Cheng Peng
Hui-Ling Lou
Feng Liu
Jie Shen
Xu Lin
Chun-Ping Zeng
Ji-Rong Long
Kuan-Jui Su
Lan Zhang
Jonathan Greenbaum
Wei-Feng Deng
Yu-Mei Li
Hong-Wen Deng
Publication date
01-11-2017
Publisher
Springer US
Published in
Calcified Tissue International / Issue 5/2017
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-017-0308-x

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