Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, College of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Osteoporos Int. 2010 May;21(5):785-95. doi: 10.1007/s00198-009-1014-y. Epub 2009 Jul 24.
Osteoporosis is a major public health problem characterized by low bone mineral density (BMD). This replication study confirmed 38 single-nucleotide polymorphisms (SNPs) out of 139 SNPs previously reported in three recent genome-wide association studies (GWASs) in an independent US white sample. Ten SNPs achieved combined p < 3.6 x 10(-4).
BMD is under strong genetic control. This study aims to verify the potential associations between BMD and candidate genes/loci reported by GWAS of FHS100K, Icelandic deCODE, and UK-NL.
Eight promising (at the genome-wide significant level after Bonferroni correction) and 131 available sub-promising (at the most stringent p value, p < 5.5 x 10(-5) in the three GWASs reports) SNPs were selected. By using genotypic information from Affymetrix 500 K SNP arrays, we tested their associations with BMD in 1,000 unrelated US whites. Fisher's combined probability method was used to quantify the overall evidence of association. BMD was measured by dual energy X-ray absorptiometry.
Two promising SNPs, rs3762397 and rs3736228, were replicated in the current study with p < 0.05. Besides, 36 sub-promising SNPs were replicated at the same significant level. Ten SNPs achieved significant combined p < 3.6 x 10(-4) (0.05/139 SNPs, corrected for multiple testing).
Osteoporosis susceptibility of 38 SNPs was replicated in 1,000 unrelated US whites. This study showed promise for replication of some initial genome-wide association signals.
骨质疏松症是一种主要的公共健康问题，其特征是骨矿物质密度（BMD）低。本复制研究在一个独立的美国白人样本中，对先前在三项最近的全基因组关联研究（GWAS）中报道的 139 个单核苷酸多态性（SNP）中的 38 个进行了确认。有 10 个 SNP 的合并 p 值<3.6×10(-4)。
BMD 受强烈的遗传控制。本研究旨在验证 FHS100K、冰岛 deCODE 和英国-NL 的 GWAS 报告的候选基因/基因座与 BMD 之间的潜在关联。
选择了 8 个有前途的（经 Bonferroni 校正后达到全基因组显著水平）和 131 个有前途的（在三个 GWAS 报告中最严格的 p 值，p<5.5×10(-5)）的 SNP。通过使用 Affymetrix 500 K SNP 芯片的基因型信息，我们检测了它们与 1000 个无关美国白人的 BMD 之间的关联。Fisher 联合概率法用于量化总体关联证据。BMD 通过双能 X 射线吸收法测量。
在当前研究中，两个有前途的 SNP（rs3762397 和 rs3736228）达到了 p<0.05 的复制水平。此外，36 个亚有前途的 SNP 在相同的显著水平上得到了复制。有 10 个 SNP 达到了显著的合并 p<3.6×10(-4)（0.05/139 个 SNP，经多重检验校正）。
在 1000 个无关的美国白人中，38 个 SNP 的骨质疏松易感性得到了复制。本研究表明，一些最初的全基因组关联信号具有复制的潜力。
