title: A bivariate whole genome linkage study identified genomic regions influencing both BMD and bone structure.
abstract: Areal BMD (aBMD) and areal bone size (ABS) are biologically correlated traits and are each important determinants of bone strength and risk of fractures. Studies showed that aBMD and ABS are genetically correlated, indicating that they may share some common genetic factors, which, however, are largely unknown. To study the genetic factors influencing both aBMD and ABS, bivariate whole genome linkage analyses were conducted for aBMD-ABS at the femoral neck (FN), lumbar spine (LS), and ultradistal (UD)-forearm in a large sample of 451 white pedigrees made up of 4498 individuals. We detected significant linkage on chromosome Xq27 (LOD = 4.89) for LS aBMD-ABS. In addition, we detected suggestive linkages at 20q11 (LOD = 3.65) and Xp11 (LOD = 2.96) for FN aBMD-ABS; at 12p11 (LOD = 3.39) and 17q21 (LOD = 2.94) for LS aBMD-ABS; and at 5q23 (LOD = 3.54), 7p15 (LOD = 3.45), Xq27 (LOD = 2.93), and 12p11 (LOD = 2.92) for UD-forearm aBMD-ABS. Subsequent discrimination analyses indicated that quantitative trait loci (QTLs) at 12p11 and 17q21 may have pleiotropic effects on aBMD and ABS. This study identified several genomic regions that may contain QTLs important for both aBMD and ABS. Further endeavors are necessary to follow these regions to eventually pinpoint the genetic variants affecting bone strength and risk of fractures.
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Liu
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
authors.forename: Yufang
authors.initials: Y
authors.lastname: Pei
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Deng
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Betty M
authors.initials: BM
authors.lastname: Drees
authors.forename: James J
authors.initials: JJ
authors.lastname: Hamilton
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*; D001842:Bone and Bones / Q000033:anatomy & histology*; D041321:Chromosomes, Human, X / Q000235:genetics; D019295:Computational Biology; D008040:Genetic Linkage; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype