Bivariate whole genome linkage analysis for femoral neck geometric parameters and total body lean mass.
A genome-wide bivariate analysis was conducted for femoral neck GPs and TBLM in a large white sample. We found QTLs shared by GPs and TBLM in the total sample and the sex-specific samples. QTLs with potential pleiotropy were also disclosed.


BACKGROUND
Previous studies have suggested that femoral neck cross-section geometric parameters (FNCS-GPs), including periosteal diameter (W), cross-sectional area (CSA), cortical thickness (CT), buckling ratio (BR), and section modulus (Z), are genetically correlated with total body lean mass (TBLM). However, the shared genetic factors between them are unknown.


METHODS
To identify the specific QTLs shared by FNCS-GPs and TBLM, we performed bivariate whole genome linkage analysis (WGLA) in a large sample of 451 white families made up of 4498 subjects.


RESULTS
Multipoint bivariate linkage analyses for 22 autosomes showed evidence of suggestive or significant linkages (thresholds of LOD = 2.3 and 3.7, respectively) to chromosomes 3q12 and 20q13 in the entire sample, 6p25 and 10q24 in women, and 4p15, 5q34-35 and 7q21 in men. Two-point linkage analyses for chromosome X showed strong linkage to Xp22.13, Xp11.4, Xq22.3, Xq23-24, and Xq25. Complete pleiotropy was identified on 10q24 and 5q35 for TBLM and BR in women and for TBLM and CT in men, respectively. Furthermore, chromosomes 5q34-35, 7q21, 10q24, 20q13, Xp22.13, Xp11.4, and Xq25 are also of importance because of their linkage to multiple trait pairs. For example, linkage to chromosome 10q24 was found for TBLM x W (LOD = 2.31), TBLM x CT (LOD = 2.51), TBLM x CSA (LOD = 2.51), TBLM x BR (LOD = 2.64), and TBLM x Z (LOD = 2.55) in women.


CONCLUSIONS
In this study, we identified several genomic regions (e.g., 3q12 and 20q13) that seem to be linked to both FNCS-GPs and TBLM. These regions are of interesting because they may harbor genes that may contribute to variation in both FNCS-GPs and TBLM.
Deng
Fei-Yan
FY
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Xiao
Peng
P
Lei
Shu-Feng
SF
Zhang
Lei
L
Yang
Fang
F
Tang
Zi-Hui
ZH
Liu
Peng-Yuan
PY
Liu
Yong-Jun
YJ
Recker
Robert R
RR
Deng
Hong-Wen
HW
D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001835:Body Weight / Q000235:genetics; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology*; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D040641:Quantitative Trait Loci / Q000235:genetics; D012737:Sex Factors; D044465:White People / Q000235:genetics