Presented in part as an abstract at the 23rd annual meeting of the American Society for Bone and Mineral Research, Phoenix, Arizona, USA, October 12–16, 2001.
Version of Record online: 1 SEP 2002
Copyright © 2002 ASBMR
Journal of Bone and Mineral Research
Volume 17, Issue 9, pages 1718–1727, September 2002
How to Cite
Karasik, D., Myers, R. H., Cupples, L. A., Hannan, M. T., Gagnon, D. R., Herbert, A. and Kiel, D. P. (2002), Genome Screen for Quantitative Trait Loci Contributing to Normal Variation in Bone Mineral Density: The Framingham Study. J Bone Miner Res, 17: 1718–1727. doi: 10.1359/jbmr.2002.17.9.1718
The authors have no conflict of interest.
- Issue online: 2 DEC 2009
- Version of Record online: 1 SEP 2002
- Manuscript Accepted: 16 APR 2002
- Manuscript Revised: 27 FEB 2002
- Manuscript Received: 19 NOV 2001
- quantitative trait loci;
- genome screen;
- variance component analysis;
- bone density;
- Framingham cohorts
A genome-wide scan was performed in a randomly ascertained set of 330 extended families from the population-based Framingham Study to identify chromosomal regions possibly linked to bone mineral density (BMD). A set of 401 microsatellite markers was typed at a 10-centimorgan (cM) average density throughout the genome. BMD was measured at the femoral neck, trochanter, Ward's area, and lumbar spine in 1557 participants of both Framingham cohorts. BMDs were adjusted for age, body mass index (BMI), height, alcohol, caffeine, calcium and vitamin D intakes, smoking, physical activity, and estrogen use in women within each sex and cohort. Strong heritabilities (values between 0.543 and 0.633) were found for the adjusted BMD at all sites. Two-point and multipoint quantitative linkage analyses were performed for each BMD site using the maximum likelihood variance components method. By two-point screening, loci of suggestive linkage were identified on chromosomes 6 and 21, with the maximum log10 of the odds ratio (LOD) scores of 2.34 for the trochanter at D21S1446 and 2.93 for the femoral neck at D6S2427. Lumbar spine BMD had maxima at D6S2427 (LOD = 1.88) and at D12S395 (LOD = 2.08). Multipoint linkage analysis revealed suggestive linkage of trochanteric BMD at a broad (∼20 cM) interval on chromosome 21q, with the peak linkage close to D21S1446 (LOD = 3.14). LOD scores were 2.13 at 8q24 with Ward's BMD and 1.92 at 14q21.3 with lumbar spine BMD. This largest genome screen to date for genes underlying normal variation in BMD, adjusted for a large number of covariates, will help to identify new positional candidate genes, otherwise unrecognized.