IL21R and PTH may underlie variation of femoral neck bone mineral density as revealed by a genome-wide association study

Yan Guo, Li Shu Zhang, Tie Lin Yang, Qing Tian, Dong Hai Xiong, Yu Fang Pei, Hong Wen Deng

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Bone mineral density (BMD) measured at the femoral neck (FN) is the most important risk phenotype for osteoporosis and has been used as a reference standard for describing osteoporosis. The specific genes influencing FN BMD remain largely unknown. To identify such genes, we first performed a genome-wide association (GWA) analysis for FN BMD in a discovery sample consisting of 983 unrelated white subjects. We then tested the top significant single-nucleotide polymorphisms (SNPs; 175 SNPs with p<5×10-4) for replication in a family-based sample of 2557 white subjects. Combing results from these two samples, we found that two genes, parathyroid hormone (PTH) and interleukin 21 receptor (IL21R), achieved consistent association results in both the discovery and replication samples. The PTH gene SNPs, rs9630182, rs2036417, and rs7125774, achieved p values of 1.10×10-4, 3.24×10-4, and 3.06×10-4, respectively, in the discovery sample; p values of 6.50×10-4, 5.08×10-3, and 5.68×10-3, respectively, in the replication sample; and combined p values of 3.98×10-7, 9.52×10-6, and 1.05×10-5, respectively, in the total sample. The IL21R gene SNPs, rs8057551, rs8061992, and rs7199138, achieved p values of 1.51×10-4, 1.53×10-4, and 3.88×10 -4, respectively, in the discovery sample; p values of 2.36×10-3, 6.74×10-3, and 6.41×10 -3, respectively, in the replication sample; and combined p values of 2.31×10-6, 8.62×10-6, and 1.41×10 -5, respectively, in the total sample. The effect size of each SNP was approximately 0.11 SD estimated in the discovery sample. PTH and IL21R both have potential biologic functions important to bone metabolism. Overall, our findings provide some new clues to the understanding of the genetic architecture of osteoporosis.

Original languageEnglish (US)
Pages (from-to)1042-1048
Number of pages7
JournalJournal of Bone and Mineral Research
Volume25
Issue number5
DOIs
StatePublished - May 2010

Keywords

  • BMD
  • Genome-wide association
  • IL21R
  • Osteoporosis
  • PTH

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Fingerprint

Dive into the research topics of 'IL21R and PTH may underlie variation of femoral neck bone mineral density as revealed by a genome-wide association study'. Together they form a unique fingerprint.

Cite this