Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites

Liang Wang, Yong Jun Liu, Peng Xiao, Hui Shen, Hong Yi Deng, Christopher J. Papasian, Betty M. Drees, James J. Hamilton, Robert R. Recker, Hong Wen Deng

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Abstract

BMDs at different skeletal sites share some common genetic determinants. Using PCA and bivariate linkage analysis, we identified a QTL on chromosome 2q32 with significant pleiotropic effects on BMDs at different skeletal sites. Introduction: BMDs at the hip, spine, and forearm are genetically correlated, suggesting the existence of quantitative trait loci (QTLs) with concurrent effects on BMDs at these three skeletal sites. Consequently, it is important to identify these QTLs in the human genome and, for those implicated QTLs, it is important to differentiate between pleiotropic effects, caused by a single gene that concurrently effects these traits, and co-incident linkage, caused by multiple, closely linked, genes that independently effect these traits. Materials and Methods: For a sample of 451 American white pedigrees made up of 4498 individuals, we evaluated the correlations between BMDs at the three skeletal sites. We carried out principal component analysis (PCA) for the three correlated traits and obtained a major component, PC1, which accounts for >75% of the co-variation of BMDs at the three sites. We subsequently conducted a whole genome linkage scan for PC1 and performed bivariate linkage analysis for pairs of the three traits (i.e., forearm/spine BMD, hip/forearm BMD, and hip/spine BMD). Results: Chromosome region 2q32, near the marker GATA65C03M, showed strong linkage to PC1 (LOD = 3.35). Subsequent bivariate linkage analysis substantiated linkage at 2q32 for each trait pair (LOD scores were 2.65, 2.42, and 2.13 for forearm/spine BMD, hip/forearm BMD, and hip/spine BMD, respectively). Further analyses rejected the hypothesis of co-incident linkage (p0[forearm/spine] = 0.0005, p0[hip/forearm] = 0.004, p0(hip/spine] = 0.001) but failed to reject the hypothesis of pleiotropy (p1 [forearm/spine] = 0.35, p1[hip/forearm] = 0.07, p1 [hip/spine] = 0.15). Conclusions: Our results strongly support the conclusion that chromosome region 2q32 may harbor a QTL with pleiotropic effects on BMDs at different skeletal sites.

Original languageEnglish
Pages (from-to)1672-1678
Number of pages7
JournalJournal of Bone and Mineral Research
Volume22
Issue number11
DOIs
StatePublished - Nov 2007

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Quantitative Trait Loci
Forearm
Hip
Spine
Chromosomes
Principal Component Analysis
Human Genome
Pedigree
Genes
Genome

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Wang, L., Liu, Y. J., Xiao, P., Shen, H., Deng, H. Y., Papasian, C. J., ... Deng, H. W. (2007). Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites. Journal of Bone and Mineral Research, 22(11), 1672-1678. https://doi.org/10.1359/jbmr.070722

Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites. / Wang, Liang; Liu, Yong Jun; Xiao, Peng; Shen, Hui; Deng, Hong Yi; Papasian, Christopher J.; Drees, Betty M.; Hamilton, James J.; Recker, Robert R.; Deng, Hong Wen.

In: Journal of Bone and Mineral Research, Vol. 22, No. 11, 11.2007, p. 1672-1678.

Research output: Contribution to journalArticle

Wang, L, Liu, YJ, Xiao, P, Shen, H, Deng, HY, Papasian, CJ, Drees, BM, Hamilton, JJ, Recker, RR & Deng, HW 2007, 'Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites', Journal of Bone and Mineral Research, vol. 22, no. 11, pp. 1672-1678. https://doi.org/10.1359/jbmr.070722
Wang, Liang ; Liu, Yong Jun ; Xiao, Peng ; Shen, Hui ; Deng, Hong Yi ; Papasian, Christopher J. ; Drees, Betty M. ; Hamilton, James J. ; Recker, Robert R. ; Deng, Hong Wen. / Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites. In: Journal of Bone and Mineral Research. 2007 ; Vol. 22, No. 11. pp. 1672-1678.
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title = "Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites",
abstract = "BMDs at different skeletal sites share some common genetic determinants. Using PCA and bivariate linkage analysis, we identified a QTL on chromosome 2q32 with significant pleiotropic effects on BMDs at different skeletal sites. Introduction: BMDs at the hip, spine, and forearm are genetically correlated, suggesting the existence of quantitative trait loci (QTLs) with concurrent effects on BMDs at these three skeletal sites. Consequently, it is important to identify these QTLs in the human genome and, for those implicated QTLs, it is important to differentiate between pleiotropic effects, caused by a single gene that concurrently effects these traits, and co-incident linkage, caused by multiple, closely linked, genes that independently effect these traits. Materials and Methods: For a sample of 451 American white pedigrees made up of 4498 individuals, we evaluated the correlations between BMDs at the three skeletal sites. We carried out principal component analysis (PCA) for the three correlated traits and obtained a major component, PC1, which accounts for >75{\%} of the co-variation of BMDs at the three sites. We subsequently conducted a whole genome linkage scan for PC1 and performed bivariate linkage analysis for pairs of the three traits (i.e., forearm/spine BMD, hip/forearm BMD, and hip/spine BMD). Results: Chromosome region 2q32, near the marker GATA65C03M, showed strong linkage to PC1 (LOD = 3.35). Subsequent bivariate linkage analysis substantiated linkage at 2q32 for each trait pair (LOD scores were 2.65, 2.42, and 2.13 for forearm/spine BMD, hip/forearm BMD, and hip/spine BMD, respectively). Further analyses rejected the hypothesis of co-incident linkage (p0[forearm/spine] = 0.0005, p0[hip/forearm] = 0.004, p0(hip/spine] = 0.001) but failed to reject the hypothesis of pleiotropy (p1 [forearm/spine] = 0.35, p1[hip/forearm] = 0.07, p1 [hip/spine] = 0.15). Conclusions: Our results strongly support the conclusion that chromosome region 2q32 may harbor a QTL with pleiotropic effects on BMDs at different skeletal sites.",
author = "Liang Wang and Liu, {Yong Jun} and Peng Xiao and Hui Shen and Deng, {Hong Yi} and Papasian, {Christopher J.} and Drees, {Betty M.} and Hamilton, {James J.} and Recker, {Robert R.} and Deng, {Hong Wen}",
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AU - Liu, Yong Jun

AU - Xiao, Peng

AU - Shen, Hui

AU - Deng, Hong Yi

AU - Papasian, Christopher J.

AU - Drees, Betty M.

AU - Hamilton, James J.

AU - Recker, Robert R.

AU - Deng, Hong Wen

PY - 2007/11

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N2 - BMDs at different skeletal sites share some common genetic determinants. Using PCA and bivariate linkage analysis, we identified a QTL on chromosome 2q32 with significant pleiotropic effects on BMDs at different skeletal sites. Introduction: BMDs at the hip, spine, and forearm are genetically correlated, suggesting the existence of quantitative trait loci (QTLs) with concurrent effects on BMDs at these three skeletal sites. Consequently, it is important to identify these QTLs in the human genome and, for those implicated QTLs, it is important to differentiate between pleiotropic effects, caused by a single gene that concurrently effects these traits, and co-incident linkage, caused by multiple, closely linked, genes that independently effect these traits. Materials and Methods: For a sample of 451 American white pedigrees made up of 4498 individuals, we evaluated the correlations between BMDs at the three skeletal sites. We carried out principal component analysis (PCA) for the three correlated traits and obtained a major component, PC1, which accounts for >75% of the co-variation of BMDs at the three sites. We subsequently conducted a whole genome linkage scan for PC1 and performed bivariate linkage analysis for pairs of the three traits (i.e., forearm/spine BMD, hip/forearm BMD, and hip/spine BMD). Results: Chromosome region 2q32, near the marker GATA65C03M, showed strong linkage to PC1 (LOD = 3.35). Subsequent bivariate linkage analysis substantiated linkage at 2q32 for each trait pair (LOD scores were 2.65, 2.42, and 2.13 for forearm/spine BMD, hip/forearm BMD, and hip/spine BMD, respectively). Further analyses rejected the hypothesis of co-incident linkage (p0[forearm/spine] = 0.0005, p0[hip/forearm] = 0.004, p0(hip/spine] = 0.001) but failed to reject the hypothesis of pleiotropy (p1 [forearm/spine] = 0.35, p1[hip/forearm] = 0.07, p1 [hip/spine] = 0.15). Conclusions: Our results strongly support the conclusion that chromosome region 2q32 may harbor a QTL with pleiotropic effects on BMDs at different skeletal sites.

AB - BMDs at different skeletal sites share some common genetic determinants. Using PCA and bivariate linkage analysis, we identified a QTL on chromosome 2q32 with significant pleiotropic effects on BMDs at different skeletal sites. Introduction: BMDs at the hip, spine, and forearm are genetically correlated, suggesting the existence of quantitative trait loci (QTLs) with concurrent effects on BMDs at these three skeletal sites. Consequently, it is important to identify these QTLs in the human genome and, for those implicated QTLs, it is important to differentiate between pleiotropic effects, caused by a single gene that concurrently effects these traits, and co-incident linkage, caused by multiple, closely linked, genes that independently effect these traits. Materials and Methods: For a sample of 451 American white pedigrees made up of 4498 individuals, we evaluated the correlations between BMDs at the three skeletal sites. We carried out principal component analysis (PCA) for the three correlated traits and obtained a major component, PC1, which accounts for >75% of the co-variation of BMDs at the three sites. We subsequently conducted a whole genome linkage scan for PC1 and performed bivariate linkage analysis for pairs of the three traits (i.e., forearm/spine BMD, hip/forearm BMD, and hip/spine BMD). Results: Chromosome region 2q32, near the marker GATA65C03M, showed strong linkage to PC1 (LOD = 3.35). Subsequent bivariate linkage analysis substantiated linkage at 2q32 for each trait pair (LOD scores were 2.65, 2.42, and 2.13 for forearm/spine BMD, hip/forearm BMD, and hip/spine BMD, respectively). Further analyses rejected the hypothesis of co-incident linkage (p0[forearm/spine] = 0.0005, p0[hip/forearm] = 0.004, p0(hip/spine] = 0.001) but failed to reject the hypothesis of pleiotropy (p1 [forearm/spine] = 0.35, p1[hip/forearm] = 0.07, p1 [hip/spine] = 0.15). Conclusions: Our results strongly support the conclusion that chromosome region 2q32 may harbor a QTL with pleiotropic effects on BMDs at different skeletal sites.

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