Background: Bone size is an important determinant of bone strength and is under strong genetic control.
Objective: To identify quantitative trait loci (QTL) for areal bone size variation, a large-scale genomewide linkage scan was carried out in 451 Caucasian families.
Participants and methods: Of 4124 people with phenotypes, 3899 were genotyped with 410 microsatellite markers. Multipoint linkage analyses were carried out in the entire sample, as well as in men and women separately. Potential epistatic interactions between identified genomic regions were also assessed.
Results: Several potentially important genomic regions were identified, such as 8q24 for hip bone size (logarithm of the ratio of the odds that two loci are linked (LOD) 3.27) and 2p24 (LOD 2.04) for spine bone size. 8q24 may also interact with 19p13 to affect hip bone size. Several sex-specific QTL were also detected, such as 14q21 (LOD 2.94) for wrist bone size in women and 16q12 (LOD 2.19) for hip bone size in men.
Conclusions: Together with previous findings, this study has further delineated the genetic basis of bone size and laid a foundation for future studies to eventually elucidate the mechanisms of bone size regulation and associated fracture risks.
- BMD, bone mineral density
- DXA, dual-energy x ray absorptiometry
- LOD, logarithm of the ratio of the odds that two loci are linked
- QTL, quantitative trait loci
- SOLAR, sequential oligogenic linkage analysis routines
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Published Online First 6 July 2006
Funding: Investigators of this work were partially supported by grants from the National Institutes of Health, Bethesda, Maryland, USA (K01 AR02170-01, R01 AR45349-01, R01 GM60402-01A1) and an LB595 grant from the state of Nebraska. The study also benefited from grants from the National Science Foundation of China, Huo Ying Dong Education Foundation, HuNan Province, Xi’an Jiaotong University and the Ministry of Education of China. The genotyping experiment was performed by the Marshfield Center for Medical Genetics and supported by NHLBI Mammalian Genotyping Service (Contract Number HV48141).
Competing interests: None.
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