Skip to main content
Article thumbnail
Location of Repository

A validation of the first genome-wide association study of calcaneus ultrasound parameters in the European Male Ageing Study

By D. Roshandel, W. Thomson, S.R. Pye, S. Boonen, H. Borghs, D. Vanderschueren, I.T. Huhtaniemi, J.E. Adams, K.A. Ward, G. Bartfai, F. Casanueva, J.D. Finn, G. Forti, A. Giwercman, T.S. Han, K. Kula, M. Lean, N. Pendleton, M. Punab, A.J. Silman, F.C. Wu, K. Holliday and T. O'Neill

Abstract

<p><b>Background</b></p>\ud \ud <p>A number of single nucleotide polymorphisms (SNPs) have been associated with broadband ultrasound attenuation (BUA) and speed of sound (SOS) as measured by quantitative ultrasound (QUS) at the calcaneus in the Framingham 100K genome-wide association study (GWAS) but have not been validated in independent studies. The aim of this analysis was to determine if these SNPs are associated with QUS measurements assessed in a large independent population of European middle-aged and elderly men. The association between these SNPs and bone mineral density (BMD) measured using dual-energy X-ray absorptiometry (DXA) was also tested.</p>\ud \ud <p><b>Methods</b></p>\ud \ud <p>Men aged 40-79 years (N = 2960) were recruited from population registers in seven European centres for participation in an observational study of male ageing, the European Male Ageing Study (EMAS). QUS at the calcaneus was measured in all subjects and blood was taken for genetic analysis. Lumbar spine (LS), femoral neck (FN) and total hip (TH) BMD were measured by DXA in a subsample of 620 men in two centres. SNPs associated with BUA or SOS in the Framingham study with p &#x3C; 10-4 were selected and genotyped using SEQUENOM technology. Linear regression was used to test for the association between SNPs and standardised (SD) bone outcomes under an additive genetic model adjusting for centre. The same direction of effect and p &#x3C; 0.05 indicated replication.</p>\ud \ud <p><b>Results</b></p>\ud \ud <p>Thirty-four of 38 selected SNPs were successfully genotyped in 2377 men. Suggestive evidence of replication was observed for a single SNP, rs3754032, which was associated with a higher SOS (&#x3B2;(SD) = 0.07, p = 0.032) but not BUA (&#x3B2;(SD) = 0.02, p = 0.505) and is located in the 3'UTR of WDR77 (WD repeat domain 77) also known as androgen receptor cofactor p44. A single SNP, rs238358, was associated with BMD at the LS (&#x3B2;(SD) = -0.22, p = 0.014), FN (&#x3B2;(SD) = -0.31,p = 0.001) and TH (&#x3B2;(SD) = -0.36, p = 0.002) in a locus previously associated with LS BMD in large-scale GWAS, incorporating AKAP11 and RANKL.</p>\ud \ud <p><b>Conclusions</b></p>\ud \ud <p>We found suggestive evidence of association between a single SNP located in the 3'UTR of WDR77 with calcaneal ultrasound parameters. The majority of SNPs, associated with QUS parameters in the Framingham Study, were not replicated in an independent population sample of European men.</p

Publisher: BioMed Central Ltd.
Year: 2011
OAI identifier: oai:eprints.gla.ac.uk:54385
Provided by: Enlighten

Suggested articles

Citations

  1. (2004). Alhava E: Calcaneal ultrasound predicts early postmenopausal fractures as well as axial BMD. A prospective study of 422 women. Osteoporos Int doi
  2. (1997). Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med doi
  3. (1993). CA: The Physical Activity Scale for the Elderly (PASE): development and evaluation. doi
  4. (2008). Distinct nuclear and cytoplasmic functions of androgen receptor cofactor p44 and association with androgen-independent prostate cancer. Proc Natl Acad Sci USA doi
  5. (2006). et al: Cross-calibration of dual-energy X-ray densitometers for a large, multicenter genetic study of osteoporosis. Osteoporos Int doi
  6. (2004). et al: Heritability of calcaneal quantitative ultrasound measures in healthy adults from the Fels Longitudinal Study. doi
  7. (2006). et al: IB-MECA, an A3 adenosine receptor agonist prevents bone resorption in rats with adjuvant induced arthritis. Clin Exp Rheumatol
  8. (2009). et al: Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment. Arthritis Rheum doi
  9. (2002). et al: Mapping of quantitative ultrasound of the calcaneus bone to chromosome 1 by genome-wide linkage analysis. Osteoporos Int doi
  10. (2008). et al: Multiple Genetic Loci for Bone Mineral Density and Fractures. doi
  11. (2007). et al: PLINK: a tool set for whole-genome association and population-based linkage analyses. doi
  12. (2009). et al: Twenty bone-mineral-density loci identified by largescale meta-analysis of genome-wide association studies. Nat Genet
  13. (1996). et al: Ultrasonographic heel measurements to predict hip fracture in elderly women: the EPIDOS prospective study. Lancet doi
  14. (2002). Gender differences in the genetic factors responsible for variation in bone density and ultrasound. J Bone Miner Res doi
  15. Karasik D: Genomewide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet 2007, 8(Suppl 1):S14. doi
  16. (2005). MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics doi
  17. (2003). Purification and identification of a novel complex which is involved in androgen receptor-dependent transcription. Mol Cell Biol doi
  18. (2006). QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies.
  19. (2005). Risk of fracture after androgen deprivation for prostate cancer. doi
  20. (2003). Spector TD: An investigation of unique and shared gene effects on speed of sound and bone density using axial transmission quantitative ultrasound and DXA in twins. J Bone Miner Res doi
  21. (1996). TD: The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.