Bone mineral density is linked to 1p36 and 7p15-13 in a southern Chinese population

Genome-wide linkage scans have identified a number of quantitative trait loci (QTLs) affecting bone mineral density (BMD), mainly in the Caucasian population. In this study, we aim to determine whether seven well-replicated QTLs also contribute to BMD variation in the southern Han Chinese population. Thirty-three microsatellite markers in the proximity of seven QTLs were genotyped in 1,459 subjects from 306 families ascertained through a proband with BMD Z-score equal to or less than –1.3 at either the lumbar spine or hip. Regression-based multipoint linkage analysis was performed. In the entire study population, good linkage evidence of total hip BMD to 7p14 [maximum log of odds (LOD) score (MLS) = 2.75; nominal P = 0.0002] and 1p36 (MLS = 1.6, P = 0.003) was revealed. In the subgroup analysis of 1,166 female subjects, MLS of 3.42, 2.65, 2.42, and 1.54 were obtained on 7p12 for total hip, lumbar spine, trochanter, and femoral neck BMD, respectively. A suggestive linkage signal was achieved at 7p14-15 with a MLS of 3.38 and 3.15 for trochanter and total hip BMD in the 678 premenopausal women, and at 7p12 for femoral neck and total hip BMD with MLS of 2.22 and 3.04 in postmenopausal women. Subgroup analysis of premenopausal women also provided additional evidence of suggestive linkage of total hip BMD to 1p36, with a MLS of 2.84 at 17.07 cM. Thus, linkage of BMD to 1p36 and 7p15-13 is confirmed in southern Chinese. Computational prioritization strategy and published genome-wide association studies suggested RERE and SFRP4 as two promising candidate genes in which variants responsible for the linkage signal may be identified by follow-up gene-wide association studies.