title: Genome scan for QTLs underlying bone size variation at 10 refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement.
abstract: To identify quantitative trait loci (QTLs) underlying variation in bone size, we conducted a whole-genome linkage scan in 53 pedigrees with 630 subjects using 380 microsatellite markers. Lumbar area 1, 2, 3, and 4 at the spine, femoral neck, trochanter, intertrochanter areas at the hip, ultradistal, mid-distal, and one-third distal areas at the wrist were measured by dual-energy X-ray absorptiometry (DXA), and adjusted for age, height, weight, and sex. Two-point and multipoint linkage analyses were performed for skeletal bone size at each site and their composite measurements using the SOLAR package. Two chromosomal regions (1q22 and 10q21) were identified with significant evidence of linkage (LOD > 4.32) to one-third distal area, and three were identified with suggestive evidence of linkage (LOD > 2.93) to bone size in one skeletal site. Our results indicated that the low power of QTLs mapping for composite phenotypic measurements may result from genetic heterogeneity of complex traits.
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, Nebraska 68131, USA.
authors.forename: Qing-Yang
authors.initials: QY
authors.lastname: Huang
authors.forename: Fu-Hua
authors.initials: FH
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Deng
authors.forename: Theresa
authors.initials: T
authors.lastname: Conway
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Li
authors.forename: Miao-Xin
authors.initials: MX
authors.lastname: Li
authors.forename: K Michael
authors.initials: KM
authors.lastname: Davies
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D001842:Bone and Bones / Q000033:anatomy & histology*; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D015894:Genome, Human; D006615:Hip; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D040641:Quantitative Trait Loci; D013131:Spine / Q000033:anatomy & histology; D014953:Wrist