Mapping of quantitative ultrasound of the calcaneus bone to chromosome 1 by genome-wide linkage analysis
Mapping of quantitative ultrasound of the calcaneus bone to chromosome 1 by genome-wide linkage analysis
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DOI：
10.1007/s001980200110
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发表时间：
2002-01-01
影响因子：
4
通讯作者：
Kiel, DP
中科院分区：
文献类型：
--
作者：
Karasik, D;Myers, RH;Kiel, DP
定量超声（QUS）可以独立于骨密度预测骨折风险。本研究的目的是确定，使用数量性状连锁分析，染色体区域，可能包含基因的影响变化，跟骨超声措施在一组家庭从一般人群。全基因组常染色体扫描进行了324个高加索家庭（1270个测量的个人）从Frachial骨质疏松症研究，使用一组401个Marshfield微卫星标记与10 cM的平均密度图。QUS测量包括宽带超声衰减（BUA）、声速（SOS）和定量超声指数2（QUI）。这些表型回归年龄，年龄，体重指数，身高，酒精和咖啡因的消费，吸烟状况，体力活动，雌激素的使用在女性中，在每个性别和代分别。调整后的QUS表型表现出较强的遗传力，范围从0.45（SOS）到0.52（BUA）。通过两点方差分量基因组筛选，在染色体区域1p36.3和5p15.2上鉴定了可能连锁的表型特异性区域。使用DIS 468（4 cM）时，BUA达到的最大LOD评分为2.74，使用D5S817（23 cM）时，SOS达到的最大LOD评分为2.69。SOS和BUA的线性组合QUI显示与两个标记连锁（与DIS 468的LOD = 2.1，与D5S817的LOD = 2.2）。两点分析的结果仅通过多点连锁分析证实了BUA，在D1S468 LOD = 2.4，但未证实SOS或QUI。除上述协变量外，经股骨和腰椎骨密度校正的QUS结果几乎相同。总之，我们的研究结果表明，可能有遗传决定因素的BUA上1p36.3。这些结果应鼓励进一步调查QUS变异性和候选多态性在该地区的遗传来源。
Quantitative ultrasound (QUS) may predict the risk of fracture independent of bone density. The aim of this study was to identify, using quantitative trait linkage analysis, chromosomal regions that might contain genes influencing variation in calcaneal ultrasound measures in a set of families from the general population. A genome-wide autosomal scan was conducted in 324 Caucasian families (1270 measured individuals) from the Framingham Osteoporosis Study, using a set of 401 Marshfield microsatellite markers with a 10 cM average density map. QUS measurements included broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index 2 (QUI). These phenotypes were regressed on age, age, body mass index, height, alcohol and caffeine consumption, smoking status, physical activity, and estrogen use in females, in each sex and generation separately. Adjusted QUS phenotypes demonstrated a strong heritability ranging from 0.45 (SOS) to 0.52 (BUA). By two-point variance components genome screening, phenotype-specific regions of possible linkage were identified on chromosomal regions 1p36.3 and 5p15.2. The maximum LOD score attained was 2.74 for BUA with DIS468 (4 cM) and 2.69 for SOS with D5S817 (23 cM). QUI, a linear combination of the SOS and BUA, showed linkage with both markers (LOD = 2.1 with DIS468 and LOD = 2.2 with D5S817). Results of two-point analysis were confirmed by multipoint linkage analysis only for BUA, with LOD = 2.4 at D1S468, but not for SOS or QUI. The results for QUS, adjusted for femoral and lumbar spinal bone mineral density, in addition to the above covariates, were virtually the same. In conclusion, our results suggest that there may be genetic determinants for BUA on 1p36.3. These results should encourage further investigations of the genetic source of QUS variability and candidate polymorphisms in this region.