Journal of Bone and Mineral Metabolism

, Volume 37, Issue 1, pp 43–52 | Cite as

Identification of pleiotropic genetic variants affecting osteoporosis risk in a Korean elderly cohort

  • Eun Pyo Hong
  • Ka Hyun Rhee
  • Dong Hyun Kim
  • Ji Wan ParkEmail author
Original Article


Pleiotropy has important implications for understanding the genetic basis and risk assessment of osteoporosis. Our aim was to identify pleiotropic genetic variants associated with the development of osteoporosis and predict osteoporosis risk by leveraging pleiotropic variants. We evaluated the effects of 21 conventional risk factors and 185 single-nucleotide polymorphisms (SNPs) in 63 inflammation- and metabolism-related genes on osteoporosis risk in a community-based Korean cohort study of 1025 participants, the Hallym Aging Study. Ten nongenetic factors, including sex (female) and hematocrit level, and 12 SNPs across ten genes showed evidence of association with incident osteoporosis in 270 initially osteoporosis-free subjects who completed a 6-year follow up. Three gene variants, rs1801282 (PPARG-Pro12Ala, hazard ratio (HR) = 3.26, P = 0.008), rs1408282 (near EPHA7, HR = 1.87, P = 0.002), and rs2076212 (PNPLA3-Gly115Cys, HR = 2.24, P = 0.024), were associated with significant differences in survival among the three genotype groups (Pdiff = 0.042, 0.003, and 0.048, respectively). Individuals in the highest polygenic risk score tertile were 27.9 fold more likely to develop osteoporosis than those in the lowest tertile (P = 0.004). The PPARG gene in particular was a hub pleiotropic gene in the epistasis network. Our findings highlight pleiotropic modulations of metabolism- and inflammation-related genes in the development of osteoporosis and demonstrate the contribution of pleiotropic genetic variants in prediction of osteoporosis risk.


Osteoporosis Pleiotropy Polygenic risk score Risk assessment Survival analysis 



This research was supported by the Basic Science Research Program of the National. Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2014R1A1A3053168), the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2012M3A9D1054450), and Hallym University Research Fund 2017 (HRF-201704-015). We are greatly thankful to all participants and staff in the Hallym Aging Study for their contribution to the project.

Compliance with ethical standards

Conflict of interest

All authors have no conflicts of interest.

Supplementary material

774_2017_892_MOESM1_ESM.docx (71 kb)
Supplementary material 1 (DOCX 71 kb)


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Copyright information

© The Japanese Society for Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Medical Genetics, College of MedicineHallym UniversityChuncheonRepublic of Korea
  2. 2.Department of Medicine, College of MedicineHallym UniversityChuncheonRepublic of Korea
  3. 3.Department of Social and Preventive Medicine, College of MedicineHallym UniversityChuncheonRepublic of Korea
  4. 4.Hallym Research Institute of Clinical EpidemiologyHallym University Sacred Heart HospitalAnyangRepublic of Korea

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