A whole genome linkage scan for QTLs underlying peak bone mineral density.
We conducted a whole genome linkage scan for quantitative trait loci (QTLs) underlying peak bone mineral density (PBMD). Our efforts identified several potential genomic regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation.


BACKGROUND
Peak bone mineral density (PBMD) is an important clinical risk predictor of osteoporosis and explains a large part of bone mineral density (BMD) variation.


METHODS
To detect susceptive quantitative trait loci (QTLs) for PBMD variation including consideration of epistatic and sex-specific effects, we conducted a whole genome linkage scan (WGLS) for PBMD using 2,200 Caucasians from 207 pedigrees, aged 20-50 years. All the individuals were genotyped with 410 microsatellite markers. In addition to WGLS in the total combined sample of males and females, we conducted epistatic interaction analyses, and sex-specific subgroup linkage analyses.


RESULTS
We identified several potential genomic regions that met the criteria for suggestive linkage. The most impressing region is 12p12 for hip PBMD (LOD = 2.79) in the total sample. Epistatic interaction analyses found a significant epistatic interaction between 12p12 and 22q13 (p = 0.0021) for hip PBMD. Additionally, we detected suggestive linkage evidence at 15q26 (LOD = 2.93), 2p13 (LOD = 2.64), and Xq27 (LOD = 2.64). Sex-specific analyses suggested the presence of sex-specific QTLs for PBMD variation.


CONCLUSIONS
Our efforts identified several potential regions for PBMD and highlighted the importance of epistatic interaction and sex-specific analyses in identifying genetic regions underlying PBMD variation.
Zhang
F
F
The Key Laboratory of Biomedical Information Engineering of the Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.
Xiao
P
P
Yang
F
F
Shen
H
H
Xiong
D-H
DH
Deng
H-Y
HY
Papasian
C J
CJ
Drees
B M
BM
Hamilton
J J
JJ
Recker
R R
RR
Deng
H-W
HW
D015502:Absorptiometry, Photon; D000328:Adult; D000886:Anthropometry; D015519:Bone Density / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D006621:Hip Joint / Q000502:physiology; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D040641:Quantitative Trait Loci; D012727:Sex Characteristics; D014955:Wrist Joint / Q000502:physiology