A follow-up linkage study for bone size variation in an extended sample.
Bone size, which has strong genetic determination, is an important determinant of bone strength and a risk factor of osteoporotic fractures. We previously reported an approximately 10-cm genome-wide linkage scan in 630 subjects from 53 US Caucasian pedigrees. The strongest evidence of linkage was obtained on chromosome 17q22 near the marker D17S787, with a two-point LOD score of 3.98 and a multipoint maximum LOD score (MLS) of 3.01. Additionally, suggestive linkages (1.54 < MLS < 2.83) were found at the other four chromosomal regions. In the present study, with an attempt to further examine our previous findings, we perform a follow-up linkage analysis in an expanded sample of 79 pedigrees with 1816 subjects. The total sample contains >80,000 informative relative pairs for linkage analyses, including 3846 sib pairs. Fifteen markers covering the above five promising regions are genotyped, narrowing the average genomic distance from approximately 10 to 5 cm. In the total 79 pedigrees, support of linkage was achieved for the wrist bone size at 17q22 with a two-point LOD score of 2.27 (P = 0.0006) and MLS of 1.78 (P = 0.002). The genomic region 17q22 includes COL1A1, a strong candidate gene that is significantly associated with osteoporotic fracture risk. Our data suggest that this region is promising for further exploratory studies.
Xu
Fu-Hua
FH
Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA.
Liu
Yong-Jun
YJ
Deng
Hongyi
H
Huang
Qing-Yang
QY
Zhao
Lan-Juan
LJ
Shen
Hui
H
Liu
Yao-Zhong
YZ
Dvornyk
Volodymyr
V
Conway
Theresa
T
Li
Jin-Long
JL
Davies
K Michael
KM
Recker
Robert R
RR
Deng
Hong-Wen
HW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D001846:Bone Development / Q000235:genetics*; D001842:Bone and Bones / Q000502:physiology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D040641:Quantitative Trait Loci