Genomic regions identified for BMD in a large sample including epistatic interactions and gender-specific effects.
A genome-wide linkage scan was conducted using a large white sample to identify QTLs for BMD. We found QTLs in the total sample and the gender-specific subgroups, as well as significant epistatic interactions underlying BMD variations.


BACKGROUND
Low BMD is an important risk factor for osteoporosis and under strong genetic control.


METHODS
To identify quantitative trait loci (QTLs) for regulation of BMD, we performed a large-scale whole genome linkage scan (WGS) involving 4126 individuals from 451 families. In addition to the conventional linkage analyses in the total combined sample of males and females, we conducted epistatic interaction analyses and gender-specific linkage analyses.


RESULTS
Significant linkage was detected on 5q23 for wrist BMD (LOD = 3.39) and 15q13 for female spine BMD (LOD = 4.49). For spine BMD, we revealed significant epistatic interactions between 3p25 and 2q32 (p = 0.0022) and between 3p25 and 11q23 (p = 0.0007). We replicated several genomic regions that showed linkage with BMD in previous studies by others and ours, such as 3p21, 1p36, and Xq27.


CONCLUSIONS
This study highlights the importance of large sample size, incorporation of epistatic interaction, and consideration of gender-specific effects in identifying QTLs for BMD variation. The results of this study provide a foundation for the future fine mapping and gene identification in our population.
Xiao
Peng
P
Department of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska, USA.
Shen
Hui
H
Guo
Yan-Fang
YF
Xiong
Dong-Hai
DH
Liu
Yao-Zhong
YZ
Liu
Yong-Jun
YJ
Zhao
Lan-Juan
LJ
Long
Ji-Rong
JR
Guo
Yan
Y
Recker
Robert R
RR
Deng
Hong-Wen
HW
D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping; D004843:Epistasis, Genetic; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008297:Male; D010375:Pedigree; D040641:Quantitative Trait Loci; D012737:Sex Factors