Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13

D. L. Koller, L. A. Rodriguez, J. C. Christian, C. W. Slemenda, M. J. Econs, S. L. Hui, P. Morin, P. M. Conneally, G. Joslyn, M. E. Curran, M. Peacock, C. C. Johnston, T. Foroud

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Abstract

Osteoporosis is a leading public health problem that is responsible for substantial morbidity and mortality. A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Recent linkage of three Mendelian BMD-related phenotypes, autosomal dominant high bone mass, autosomal recessive osteoporosis- pseudoglioma, and autosomal recessive osteopetrosis to chromosome 11q12-13 led us to evaluate this region to determine if the underlying gene(s) could also contribute to variation in BMD in the normal population. We performed a linkage study in a sample of 835 premenopausal Caucasian and African-American sisters to identify genes underlying BMD variation. A maximum multipoint LOD score of 3.50 with femoral neck BMD was obtained near the marker D11S987, in the same chromosomal region as the three Mendelian traits mentioned above. Our results suggest that the gene(s) underlying these Mendelian phenotypes also play a role in determining peak BMD in the normal population and are the first using linkage methods to establish a chromosomal location for a gene important in determining peak BMD. These findings support the hypothesis that a gene responsible for one or more of the rare Mendelian BMD traits linked to chromosome 11q12-13 has an important role in osteoporosis in the general population.

Original languageEnglish (US)
Pages (from-to)1903-1908
Number of pages6
JournalJournal of Bone and Mineral Research
Volume13
Issue number12
DOIs
StatePublished - Dec 1998

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Chromosomes, Human, Pair 13
Bone Density
Osteoporosis
Genes
Population
Osteopetrosis
Phenotype
Femur Neck
African Americans
Siblings
Public Health
Morbidity
Bone and Bones
Mortality

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13. / Koller, D. L.; Rodriguez, L. A.; Christian, J. C.; Slemenda, C. W.; Econs, M. J.; Hui, S. L.; Morin, P.; Conneally, P. M.; Joslyn, G.; Curran, M. E.; Peacock, M.; Johnston, C. C.; Foroud, T.

In: Journal of Bone and Mineral Research, Vol. 13, No. 12, 12.1998, p. 1903-1908.

Research output: Contribution to journalArticle

Koller, DL, Rodriguez, LA, Christian, JC, Slemenda, CW, Econs, MJ, Hui, SL, Morin, P, Conneally, PM, Joslyn, G, Curran, ME, Peacock, M, Johnston, CC & Foroud, T 1998, 'Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13', Journal of Bone and Mineral Research, vol. 13, no. 12, pp. 1903-1908. https://doi.org/10.1359/jbmr.1998.13.12.1903
Koller, D. L. ; Rodriguez, L. A. ; Christian, J. C. ; Slemenda, C. W. ; Econs, M. J. ; Hui, S. L. ; Morin, P. ; Conneally, P. M. ; Joslyn, G. ; Curran, M. E. ; Peacock, M. ; Johnston, C. C. ; Foroud, T. / Linkage of a QTL contributing to normal variation in bone mineral density to chromosome 11q12-13. In: Journal of Bone and Mineral Research. 1998 ; Vol. 13, No. 12. pp. 1903-1908.
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