J Med Genet 41:743-751 doi:10.1136/jmg.2004.020396
  • Original article

A genome-wide linkage scan for bone mineral density in an extended sample: evidence for linkage on 11q23 and Xq27

  1. H Shen1,
  2. Y-Y Zhang1,
  3. J-R Long1,
  4. F-H Xu1,
  5. Y-Z Liu1,
  6. P Xiao1,
  7. L-J Zhao1,
  8. D-H Xiong1,
  9. Y-J Liu1,
  10. V Dvornyk1,
  11. S Rocha-Sanchez2,
  12. P-Y Liu1,
  13. J-L Li3,
  14. T Conway1,
  15. K M Davies1,
  16. R R Recker1,
  17. H-W Deng1
  1. 1Osteoporosis Research Center, Creighton University, Omaha, Nebraska, USA
  2. 2Department of Biomedical Sciences, Creighton University
  3. 3Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516, USA
  1. Correspondence to:
 Dr Hong-Wen Deng
 Osteoporosis Research Center, 601 N 30th St, Suite 6787, Omaha, NE 68131, USA;
  • Received 28 April 2004
  • Accepted 19 May 2004


Background: Osteoporosis is a major public health problem, mainly quantified by low bone mineral density (BMD). The majority of BMD variation is determined by genetic effects. A pilot whole genome linkage scan (WGS) was previously reported in 53 white pedigrees with 630 subjects. Several genomic regions were suggested to be linked to BMD variation.

Objective: To substantiate these previous findings and detect new genomic regions.

Methods: A WGS was conducted on an extended sample where the size was almost tripled (1816 subjects from 79 pedigrees). All the subjects were genotyped with 451 microsatellite markers spaced ∼8.1 cM apart across the human genome. Two point and multipoint linkage analyses were carried out using the variance component method.

Results: The strongest linkage signal was obtained on Xq27 with two point LOD scores of 4.30 for wrist BMD, and 2.57 for hip BMD, respectively. Another important region was 11q23, which achieved a maximum LOD score of 3.13 for spine BMD in multipoint analyses, confirming the results on this region in two earlier independent studies. Suggestive linkage evidence was also found on 7p14 and 20p12.

Conclusions: Together with the findings from other studies, the current study has further delineated the genetic basis of bone mass and highlights the importance of increasing sample size to confirm linkage findings and to identify new regions of linkage.


  • Conflicts of interest: none declared

  • H Shen and Y-Y Zhang contributed equally to this work