Identification of QTL genes for BMD variation using both linkage and gene-based association approaches

Gloria Hoi Yee Li, Ching Lung Cheung, Su Mei Xiao, Kam Shing Lau, Yi Gao, Cora H. Bow, Qing Yang Huang, Pak Chung Sham, Annie Wai Chee Kung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

8 Citations (Scopus)

Abstract

Low bone mineral density (BMD) is a risk factor for osteoporotic fracture with a high heritability. Previous large scale linkage study in Northern Chinese has identified four significant quantitative trait loci (QTL) for BMD variation on chromosome 2q24, 5q21, 7p21 and 13q21. We performed a replication study of these four QTL in 1,459 Southern Chinese from 306 pedigrees. Successful replication was observed on chromosome 5q21 for femoral neck BMD with a LOD score of 1.38 (nominal p value = 0.006). We have previously identified this locus in a genome scan meta-analysis of BMD variation in a white population. Subsequent QTL-wide gene-based association analysis in 800 subjects with extreme BMD identified CAST and ERAP1 as novel BMD candidate genes (empirical p value of 0.032 and 0.014, respectively). The associations were independently replicated in a Northern European population (empirical p value of 0.01 and 0.004 for CAST and ERAP1, respectively). These findings provide further evidence that 5q21 is a BMD QTL, and CAST and ERAP1 may be associated with femoral neck BMD variation.

Original languageEnglish
Pages (from-to)539-546
Number of pages8
JournalHuman Genetics
Volume130
Issue number4
Early online date19 Mar 2011
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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