Identification of Evidence Suggestive of an Association with Peripheral Arterial Disease at the OSBPL10 Locus by Genome-Wide Investigation in the Japanese Population
Identification of Evidence Suggestive of an Association with Peripheral Arterial Disease at the OSBPL10 Locus by Genome-Wide Investigation in the Japanese Population
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DOI：
10.5551/jat.4291
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发表时间：
2010-01-01
影响因子：
4.4
通讯作者：
Morishita, Ryuichi
中科院分区：
文献类型：
--
作者：
Koriyama, Hiroshi;Nakagami, Hironori;Morishita, Ryuichi
目的：外周动脉疾病（PAD）是心血管发病的常见原因，也是心血管死亡率的独立预测因素。然而，人们对 PAD 的遗传基础知之甚少。为了阐明这一点，我们在日本个体中进行了一项两阶段的全基因组关联研究。方法：我们最初测试了 222,285 个单核苷酸多态性 (SNP)。在对 195 名 PAD 病例和 1,358 名对照者进行第一次筛查后，在第二次筛查中使用另一组 699 名 PAD 病例和 1,540 名对照者对 2,696 个 SNP (1.2%) 进行了进一步的基因分型。在这两次筛查中，对照组都是患有 PAD 以外的某些疾病的受试者。 结果：在组合组中进行分析时，在 OSBPL10 内含子的 rs1902341 处观察到 PAD 关联的最强信号（趋势检验 p=4.7E-7；OR=1.31，95% CI 1.18-1.46）。此外，PAD 与其他几个位点有一定关联，例如 CSMD1 中的 rs2554503（p=5.7E-5；OR=1.32，95% CI 1.15-1.51）或 VSP13D 中的 rs235243（p=0.04；OR=1.18，95% CI 1.01-1.37）。结论：我们的全基因组探索发现OSBPL10 基因座上 PAD 关联的提示性证据。由于该关联尚未达到全基因组显着水平，因此需要进一步的复制研究以在日本人群中进行验证。
Aim: Peripheral arterial disease (PAD) is a common cause of cardiovascular morbidity and an independent predictor of cardiovascular mortality. However, little is known about the genetic basis of PAD. To elucidate this, we performed a two-staged genome-wide association study in Japanese individuals.Methods: We initially tested 222,285 single-nucleotide polymorphisms (SNPs). After the first screening in a panel of 195 PAD cases and 1,358 controls, 2,696 SNPs (1.2%) were further genotyped in the second screening using another panel of 699 PAD cases and 1540 controls. In both screenings, controls were subjects affected with some diseases other than PAD.Results: When analyzed in the combined panel, the strongest signal of PAD association was observed at rs1902341 in the intron of OSBPL10 (p=4.7E-7 for trend test; OR=1.31, 95% CI 1.18-1.46). Also, PAD was modestly associated at several other loci such as rs2554503 in CSMD1 (p=5.7E-5; OR=1.32, 95% CI 1.15-1.51) or rs235243 in VSP13D (p=0.04; OR=1.18, 95% CI 1.01-1.37).Conclusion: Our genome-wide exploration identified suggestive evidence of PAD association at the OSBPL10 locus. Because the association has not reached a genome-wide significant level, further replication study is warranted for verification in the Japanese population.