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 language | English |
|---|---|
| Pages (from-to) | 1672-1678 |
| Number of pages | 7 |
| Journal | Journal of Bone and Mineral Research |
| Volume | 22 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2007 |
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All Science Journal Classification (ASJC) codes
- Surgery
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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 journal › Article
}
TY - JOUR
T1 - Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites
AU - Wang, Liang
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
Y1 - 2007/11
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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UR - http://www.scopus.com/inward/citedby.url?scp=38449090321&partnerID=8YFLogxK
U2 - 10.1359/jbmr.070722
DO - 10.1359/jbmr.070722
M3 - Article
C2 - 17680728
AN - SCOPUS:38449090321
VL - 22
SP - 1672
EP - 1678
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 11
ER -