Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis
Genome screen for QTLs contributing to normal variation in bone mineral density and osteoporosis
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DOI：
10.1210/jc.85.9.3116
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发表时间：
2000-09-01
影响因子：
5.8
通讯作者：
Foroud, T
中科院分区：
文献类型：
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作者：
Koller, DL;Econs, MJ;Foroud, T
骨质疏松症风险的一个主要决定因素是峰值骨密度(BMD)，这在很大程度上是由遗传因素决定的。MIE最近报道了一大批健康姐妹对的峰值骨密度与染色体11q12-13的连锁。为了确定峰值骨密度正常变异的其他基因座，我们对429对高加索姐妹对进行了常染色体基因组筛查。计算四个骨骼部位骨密度的多点LOD评分。在595对姐妹配对(464名高加索人和131名非裔美国人)中，进一步寻找LOD评分在1.85以上的染色体区域，扩展样本获得的最高LOD评分为3.86，位于染色体1q21-23，伴有腰椎骨密度。染色体5q33-35显示股骨颈骨密度的LOD评分为2.23。在染色体6p11-12,464对高加索人对的腰椎骨密度的LOD评分达到2.13。11q12-13区域内的标记继续支持与股骨颈骨密度的连锁，尽管在595对同胞样本中最高LOD评分降至2.16。我们的研究是迄今为止对峰值骨密度变异基因进行的最大规模的基因组筛查，代表了在普通人群中识别导致骨质疏松症的基因的重要一步。
A major determinant of the risk for osteoporosis is peak bone mineral density (BMD), which is largely determined by genetic factors. mie recently reported linkage of peak BMD in a large sample of healthy sister pairs to chromosome 11q12-13. To identify additional loci underlying normal variations in peak BMD, we conducted an autosomal genome screen in 429 Caucasian sister pairs. Multipoint LOD scores were computed for BMD at four skeletal sites. Chromosomal regions with LOD scores above 1.85 were further pursued in an expanded sample of 595 sister pairs (464 Caucasians and 131 African-Americans).The highest LOD score attained in the expanded sample was 3.86 at chromosome 1q21-23 with lumbar spine BMD. Chromosome 5q33-35 gave a LOD score of 2.23 with femoral neck BMD. At chromosome 6p11-12, the 464 Caucasian pairs achieved a LOD score of 2.13 with lumbar spine BMD. Markers within the 11q12-13 region continued to support linkage to femoral neck BMD, although the peak LOD score was decreased to 2.16 in the sample of 595 sibling pairs. Our study is the largest genome screen to date for genes underlying variations in peak BMD and represents an important step toward identifying genes contributing to osteoporosis in the general population.