Koller DL, White KE, Liu G, Hui SL, Conneally PM, Johnston CC, Econs MJ, Foroud T, Peacock M.
Linkage of structure at the proximal femur to chromosomes 3, 7, 8, and 19. J Bone Miner Res.
2003;18(6):1057-65.
Risk for osteoporotic fracture is determined in part by femoral structure, which is under genetic control. We conducted
a genome scan in 638 sister-pairs for structure phenotypes. Significant evidence of linkage was detected with several
chromosomal regions, including confirmation of our prior linkage findings. Bone strength and resistance to fracture at
the proximal femur is determined in part by structural variables. We previously reported that several structural variables,
including pelvic axis length, femur axis length, femur head width, and femur midshaft width, had significant or suggestive
linkage to regions of chromosomes 3, 4, 5, 7, 9, 17, and 19 in a sample of 309 white premenopausal sister pairs. We now
report the results of a genome-wide linkage analysis of femoral structure variables in 437 white and 201 black healthy
premenopausal sister pairs, of which 191 white pairs overlapped with our previously published sample. Multipoint quantitative
linkage analysis was performed using microsatellite markers genotyped throughout the genome. In the current sample, linkage
of femoral structure to chromosomes 3, 7, and 19 was confirmed in the white sister pairs, and a new linkage to chromosome 8
was identified. There was linkage at chromosome 3 to femoral head width (logarithm of the odds [LOD] = 5.0) and femur shaft
width (LOD = 3.6). On chromosome 19, there was linkage to femoral neck axis length (LOD = 3.2); on chromosome 7, to femoral
head width (LOD = 5.0); and on chromosome 8, to femoral head width (LOD = 6.0). The current findings emphasize the importance
of increasing sample size to replicate linkage findings and identify new regions of linkage.
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