期刊
JOURNAL OF BONE AND MINERAL RESEARCH
卷 23, 期 3, 页码 447-452出版社
WILEY
DOI: 10.1359/JBMR.071033
关键词
BMD; total body lean mass; genetic correlation; bivariate linkage analysis; whole genome linkage scan
资金
- NHLBI NIH HHS [N01HV48141, HV48141] Funding Source: Medline
- NIAMS NIH HHS [P50 AR055081, K01 AR002170, R01 AR45349-01, K01 AR02170-01] Funding Source: Medline
- NIA NIH HHS [R01 AG026564, R21 AG027110, R01 AG 026564-01A2, R21 AG 027110-01A1] Funding Source: Medline
- NIGMS NIH HHS [R01 GM060402, R01 GM60402-01A1] Funding Source: Medline
A genome-wide bivariate analysis was conducted for TBLM and BMD at the spine and hip in a large white sample. We found some QTLs shared by TBLM and BMD in the entire sample and the sex-specific subgroups, and QTLs with potential pleiotropy were disclosed. Introduction: Previous studies suggested that total body lean mass (TBLM) and BMD are highly genetically correlated. However, the specific shared genetic factors between TBLM and BMD are unknown. Materials and Methods: To identify the specific quantitative trait loci (QTLs) shared by TBLM and BMD at the spine (L-1-L-4) and total hip, we performed bivariate whole genome linkage analysis (WGLA) in a large sample involving 4498 white subjects of European origin. Results: Multipoint bivariate linkage analyses for 22 autosomes showed evidence of significant linkage with an LOD score of 4.86 at chromosome region 15q13 for TBLM and spine BMD in women, and suggestive linkage findings (LOD > 2.2) at 7p22 for TBLM and spine BMD for the entire sample, at 7q32 for TBLM and BMD at both spine and hip in women, and at 7q21 and 13p11 for TBLM and BMD at both spine and hip in men. Two-point linkage analyses for chromosome X also showed significant linkage signals at several regions such as Xq25. Complete pleiotropy (a single locus influencing both traits) was suggested at 7q32 and 13q11 for TBLM and BMD. Additionally, complete co-incident linkage (separate tightly clustered loci each influencing a single trait) was detected at 7p22 for TBLM and spine BMD. Conclusions: We identified several genomic regions shared by TBLM and BMD in whites. Further studies may focus on fine mapping and identification of the specific QTLs in these candidate genomic regions.
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