Genome-wide association study identifies HMGN3 locus for spine bone size variation in Chinese

Hum Genet. 2012 Mar;131(3):463-9. doi: 10.1007/s00439-011-1093-7. Epub 2011 Sep 25.

Abstract

Bone size (BS) is one of the major risk factors for osteoporotic fractures. BS variation is genetically determined to a substantial degree with heritability over 50%, but specific genes underlying variation of BS are still largely unknown. To identify specific genes for BS in Chinese, initial genome-wide association scan (GWAS) study and follow-up replication study were performed. In initial GWAS study, a group of 12 contiguous single-nucleotide polymorphism (SNP)s, which span a region of ~25 kb and locate at the upstream of HMGN3 gene (high-mobility group nucleosomal binding domain 3), achieved moderate association signals for spine BS, with P values ranging from 6.2E-05 to 1.8E-06. In the follow-up replication study, eight of the 12 SNPs were detected suggestive replicate associations with BS in 1,728 unrelated female Caucasians, which have well-known differences from Chinese in ethnic genetic background. The SNPs in the region of HMGN3 gene formed a tightly combined haplotype block in both Chinese and Caucasians. The results suggest that the genomic region containing HMGN3 gene may be associated with spine BS in Chinese.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics*
  • Female
  • Genome-Wide Association Study
  • HMGN Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Spine / anatomy & histology*

Substances

  • HMGN Proteins
  • HMGN3 protein, human