Osteoporosis International

, Volume 24, Issue 10, pp 2603–2610

Replication of Caucasian loci associated with bone mineral density in Koreans

Original Article



Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs.


Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples.


A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10−8) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10−5. After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis.


Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10−5, 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta).


Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.


Bone density Genetic loci Osteoporosis Replication SNP 

Supplementary material

198_2013_2354_MOESM1_ESM.xlsx (168 kb)
ESM 1(XLSX 168 kb)

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2013

Authors and Affiliations

  1. 1.Department of Internal MedicineSeoul National University College of MedicineSeoulKorea
  2. 2.Department of Internal MedicineChungbuk National University HospitalCheongjuKorea
  3. 3.Center for Genome Science, Korean National Institute of HealthCheongwon-gunKorea
  4. 4.Department of Preventive MedicineAjou University School of MedicineSuwonKorea

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