title: Genomic regions identified for BMD in a large sample including epistatic interactions and gender-specific effects.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences and Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Long
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: 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