Genome scan for QTLs underlying bone size variation at 10 refined skeletal sites: genetic heterogeneity and the significance of phenotype refinement.
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.
Huang
Qing-Yang
QY
Osteoporosis Research Center, Creighton University, Omaha, Nebraska 68131, USA.
Xu
Fu-Hua
FH
Shen
Hui
H
Deng
Hong-Yi
HY
Conway
Theresa
T
Liu
Yong-Jun
YJ
Liu
Yao-Zhong
YZ
Li
Jin-Long
JL
Li
Miao-Xin
MX
Davies
K Michael
KM
Recker
Robert R
RR
Deng
Hong-Wen
HW
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