Variance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p36
Variance component linkage analysis indicates a QTL for femoral neck bone mineral density on chromosome 1p36
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DOI：
10.1093/hmg/10.21.2447
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发表时间：
2001-10-02
影响因子：
3.5
通讯作者：
Spotila, LD
中科院分区：
文献类型：
--
作者：
Devoto, M;Specchia, C;Spotila, LD
骨质疏松症是一种常见疾病，其特征是骨骼强度降低和骨折易感性增加。 800万50岁以上的美国人患有股骨颈骨质疏松症。骨质疏松症最重要的危险因素是骨矿物质密度 (BMD) 低，一些流行病学研究表明遗传因素在决定 BMD 变异性方面的重要性。对七个大谱系的初步基因组筛选表明，股骨颈易受低 BMD 影响的候选区域位于染色体 1p36 上。现在，我们通过在 42 个家族的扩展样本中分析跨候选区域 40 cM 间隔的 9 个微卫星标记，证实并扩展了这一发现。在考虑了年龄、性别、体重指数、身高和体重的影响后，这些家庭的股骨颈 BMD 遗传力估计为 0.51 +/- 0.13。方差分量连锁分析得出股骨颈 BMD 与位于标记 D1S214 附近的数量性状基因座 (QTL) 连锁的最大多点 LOD 得分为 3.53。模拟分析的相关经验 P 值等于 0.0001。结果有力地支持了控制股骨颈BMD的主要QTL位于染色体1p36.2-p36.3上的假设，并且有必要对该区域的候选基因进行进一步分析。
Osteoporosis is a common condition characterized by reduced skeletal strength and increased susceptibility to fracture. Eight million Americans over the age of 50 have osteoporosis of the femoral neck. The most important risk factor for osteoporosis is low bone mineral density (BMD), and several epidemiological studies have shown the importance of genetic factors in determining variability of BMD. An initial genome screen in seven large pedigrees suggested that a candidate region conferring susceptibility to low BMD of the femoral neck was located on chromosome 1p36. We have now confirmed and extended this finding by analyzing nine microsatellite markers spanning a 40 cM interval across the candidate region in an expanded sample of 42 families. Heritability of femoral neck BMD was estimated as 0.51 +/- 0.13 in these families, after accounting for the effects of age, sex, body mass index, height and weight. Variance component linkage analysis yielded a maximum multipoint LOD score of 3.53 for linkage of femoral neck BMD to a quantitative trait locus (QTL) located near marker D1S214. The associated empirical P-value by simulation analysis was equal to 0.0001. The results strongly support the hypothesis that a major QTL controlling femoral neck BMD is located on chromosome 1p36.2-p36.3, and further analysis of candidate genes in this region is warranted.