Bone mineral density variation in men is influenced by sex-specific and non sex-specific quantitative trait loci

Munro Peacock, Daniel L. Koller, Dongbing Lai, Siu Hui, Tatiana Foroud, Michael Econs

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Introduction: A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods: aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results: A genome wide scan identified significant QTL (LOD > 3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosomes 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions: This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to the spine and five were linked to the hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.

Original languageEnglish
Pages (from-to)443-448
Number of pages6
JournalBone
Volume45
Issue number3
DOIs
StatePublished - Sep 2009

Fingerprint

Quantitative Trait Loci
Bone Density
Hip
Siblings
Spine
Chromosomes
Genome
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 21
Osteoporotic Fractures
Chromosomes, Human, Pair 7
Genes
Osteoporosis

Keywords

  • Bone mineral density
  • Genome wide scan
  • Linkage
  • Men
  • Sex-specific QTL

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Bone mineral density variation in men is influenced by sex-specific and non sex-specific quantitative trait loci. / Peacock, Munro; Koller, Daniel L.; Lai, Dongbing; Hui, Siu; Foroud, Tatiana; Econs, Michael.

In: Bone, Vol. 45, No. 3, 09.2009, p. 443-448.

Research output: Contribution to journalArticle

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abstract = "Introduction: A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods: aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results: A genome wide scan identified significant QTL (LOD > 3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosomes 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions: This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to the spine and five were linked to the hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.",
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AU - Foroud, Tatiana

AU - Econs, Michael

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N2 - Introduction: A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods: aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results: A genome wide scan identified significant QTL (LOD > 3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosomes 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions: This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to the spine and five were linked to the hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.

AB - Introduction: A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods: aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results: A genome wide scan identified significant QTL (LOD > 3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosomes 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions: This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to the spine and five were linked to the hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis.

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