Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q

Braxton D. Mitchell, Shelley A. Cole, Richard L Bauer, Stephen J. Iturria, Edgar A. Rodriguez, John Blangero, Jean W. MacCluer, James E. Hixson

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Osteocalcin (OC) is an important constituent of bone that is synthesized by osteoblasts. Serum levels of OC have been used as a biochemical marker of bone turnover. To identify the genes influencing variation in serum OC levels, we conducted a genome-wide scan in 429 individuals comprising 10 large multigenerational families. OC levels were measured by immunoassay, and genetic markers were typed at approximately 10-cM intervals across the genome. Quantitative trait linkage was tested using a multipoint analysis based on variance component methodology, adjusting for the effects of age, sex, and oral contraceptive use. Significance levels for linkage were obtained empirically, by Monte Carlo simulation. The heritability of OC levels in this population was 62 ± 8%. We detected significant evidence for linkage between a quantitative trait locus influencing serum OC levels and markers on chromosome 16q, and suggestive evidence for linkage of OC levels with markers on chromosome 20q. The multipoint lod scores peaked at 3.35 on chromosome 16 and 2.78 on chromosome 20, corresponding to P values of 0.00004 and 0.00017, respectively. A potential candidate gene for bone formation in the linked region on chromosome 20 is CDMP1, which encodes cartilage-derived morphogenetic protein 1. Future studies should evaluate whether variation in CDMP1 or in other genes in the linked regions on chromosomes 16 and 20 influence the rate of bone turnover.

Original languageEnglish (US)
Pages (from-to)1362-1366
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number4
DOIs
StatePublished - 2000

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Osteocalcin
Chromosomes
Genetic Markers
Genes
Chromosomes, Human, Pair 20
Serum
Bone
Chromosomes, Human, Pair 16
Bone Remodeling
Growth Differentiation Factor 5
Genome
Lod Score
Quantitative Trait Loci
Osteoblasts
Oral Contraceptives
Immunoassay
Osteogenesis
Biomarkers
Bone and Bones
Population

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Mitchell, B. D., Cole, S. A., Bauer, R. L., Iturria, S. J., Rodriguez, E. A., Blangero, J., ... Hixson, J. E. (2000). Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q. Journal of Clinical Endocrinology and Metabolism, 85(4), 1362-1366. https://doi.org/10.1210/jc.85.4.1362

Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q. / Mitchell, Braxton D.; Cole, Shelley A.; Bauer, Richard L; Iturria, Stephen J.; Rodriguez, Edgar A.; Blangero, John; MacCluer, Jean W.; Hixson, James E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 85, No. 4, 2000, p. 1362-1366.

Research output: Contribution to journalArticle

Mitchell, BD, Cole, SA, Bauer, RL, Iturria, SJ, Rodriguez, EA, Blangero, J, MacCluer, JW & Hixson, JE 2000, 'Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q', Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 4, pp. 1362-1366. https://doi.org/10.1210/jc.85.4.1362
Mitchell, Braxton D. ; Cole, Shelley A. ; Bauer, Richard L ; Iturria, Stephen J. ; Rodriguez, Edgar A. ; Blangero, John ; MacCluer, Jean W. ; Hixson, James E. / Genes influencing variation in serum osteocalcin concentrations are linked to markers on chromosomes 16q and 20q. In: Journal of Clinical Endocrinology and Metabolism. 2000 ; Vol. 85, No. 4. pp. 1362-1366.
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