Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women
Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women
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DOI：
10.1359/jbmr.080509
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发表时间：
2008-10-01
影响因子：
6.2
通讯作者：
Econs, Michael J.
中科院分区：
文献类型：
--
作者：
Ichikawa, Shoji;Koller, Daniel L.;Econs, Michael J.
骨质疏松症是一种复杂的疾病，遗传和环境的危险因素。骨质疏松性骨折的一个主要决定因素是在青年期获得的峰值BMD。我们先前报道了健康绝经前白色妇女的染色体1 q（LOD = 4.3）与脊柱区域BMD变化的连锁。在这项研究中，我们使用了两阶段基因分型的方法，以确定基因的连锁区域，有助于股骨颈和腰椎区域BMD的变化。在第一阶段，在1309名绝经前白色妇女的样本中，对连锁区域的654个SNP进行基因分型。与腰椎相关的最显著证据（p = 1.3 x 10（-6））是GATAD 2B基因中的rs 1127091。在第二阶段，在1692名白色女性的扩大样本中，对该候选基因周围的52个SNP进行基因分型。在一个230-kb连锁不平衡（LD）区组中，观察到8个SNPs与脊柱BMD（p < 10（-5）），以及在较小程度上与股骨颈BMD相关的显著证据。最显著的SNP（p = 3.4 x 10（-7））解释了这些妇女脊柱BMD变化的2.5%。230-kb LD块包含11个基因，但由于广泛的LD，导致BMD变异的特定基因无法确定。总之，脊柱骨密度和染色体1 q上230 kb LD区SNP之间的显著相关性表明，该区域的遗传因素在健康绝经前白色女性脊柱骨密度峰值中起重要作用。
Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 x 10(-6)) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10(-5)), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 x 10(-7)) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factors(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.