Bivariate whole genome linkage analyses for total body lean mass and BMD.
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.


BACKGROUND
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.


METHODS
To identify the specific quantitative trait loci (QTLs) shared by TBLM and BMD at the spine (L1-L4) 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.
Wang
Xiang-Li
XL
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Deng
Fei-Yan
FY
Tan
Li-Jun
LJ
Deng
Hong-Yi
HY
Liu
Yao-Zhong
YZ
Papasian
Christopher J
CJ
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D006615:Hip; D006801:Humans; D008126:Lod Score; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D044465:White People / Q000235:genetics