Sibling pair linkage and association studies between bone mineral density and the insulin-like growth factor I gene locus.
A major determinant of the risk for osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. BMD is a complex trait that presumably is influenced by multiple genes. Insulin-like growth factor I (IGF-I) is an attractive candidate gene for osteoporosis susceptibility, because IGF-I has marked effects on bone cells and has been implicated in the pathogenesis of osteoporosis. The IGF-I gene contains a microsatellite repeat polymorphism approximately 1 kb upstream from the IGF-I gene transcription start site, and previous investigators have found a higher prevalence of the 192/192 genotype of this polymorphism among men with idiopathic osteoporosis compared to controls. In this study we used this IGF-I polymorphism to test for an association between this polymorphism and BMD in our large population of premenopausal women (1 sister randomly chosen from 292 Caucasian and 71 African-American families). We also used this polymorphism to detect linkage to BMD elsewhere in the IGF-I gene or in a nearby gene using sibling pair linkage analysis in healthy premenopausal sister pairs (542 sibling pairs: 418 Caucasian and 124 African-American). Neither test provided any evidence of linkage or association between the IGF-I gene locus and spine or femoral neck BMD in Caucasians or African-Americans.
Takacs
I
I
Department of Medicine, Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202, USA.
Koller
D L
DL
Peacock
M
M
Christian
J C
JC
Hui
S L
SL
Conneally
P M
PM
Johnston
C C
CC
Foroud
T
T
Econs
M J
MJ
D000328:Adult; D015519:Bone Density / Q000235:genetics*; D005260:Female; D005269:Femur; D020022:Genetic Predisposition to Disease; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009679:Nuclear Family; D010024:Osteoporosis / Q000235:genetics; D011110:Polymorphism, Genetic; D013131:Spine
D007334:Insulin-Like Growth Factor I