Identification of a novel uterine leiomyoma GWAS locus in a Japanese population
Identification of a novel uterine leiomyoma GWAS locus in a Japanese population
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DOI：
10.1038/s41598-020-58066-8
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发表时间：
2020-01-27
影响因子：
4.6
通讯作者：
Matsuda, Koichi
中科院分区：
文献类型：
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作者：
Sakai, Kensuke;Tanikawa, Chizu;Matsuda, Koichi
子宫平滑肌瘤是最常见的妇科良性肿瘤之一，但其遗传基础仍不清楚。此前的六次GWAS共确定了33个遗传因素。在这里，我们使用来自日本人群的13，746例病例和70，316例对照进行了两阶段GWAS，然后使用3，483例病例和4，795例对照进行了重复分析。分析确定了9个显著位点，包括12q23.2上的一个新位点（rs 17033114，P=6.12x10（-25），OR为1.177（1.141-1.213），LINC 00485）。亚组分析显示，5个位点（3q26.2、5p15.33、10q24.33、11p15.5、13q14.11）在多发性平滑肌瘤中有统计学意义，2个位点（3q26.2、10q24.33）在粘膜下平滑肌瘤中有统计学意义。多效性分析表明，所有9个基因座与至少一种增殖性疾病，这表明这些基因座在共同的肿瘤途径的作用。此外，rs 2251795（3q26.2）的风险T等位基因与正常和肿瘤组织中较长的端粒长度相关。我们的研究结果阐明了遗传因素在平滑肌瘤发病机制中的重要性。
Uterine leiomyoma is one of the most common gynaecologic benign tumours, but its genetic basis remains largely unknown. Six previous GWAS identified 33 genetic factors in total. Here, we performed a two-staged GWAS using 13,746 cases and 70,316 controls from the Japanese population, followed by a replication analysis using 3,483 cases and 4,795 controls. The analysis identified 9 significant loci, including a novel locus on 12q23.2 (rs17033114, P=6.12x10(-25) with an OR of 1.177 (1.141-1.213), LINC00485). Subgroup analysis indicated that 5 loci (3q26.2, 5p15.33, 10q24.33, 11p15.5, 13q14.11) exhibited a statistically significant effect among multiple leiomyomas, and 2 loci (3q26.2, 10q24.33) exhibited a significant effect among submucous leiomyomas. Pleiotropic analysis indicated that all 9 loci were associated with at least one proliferative disease, suggesting the role of these loci in the common neoplastic pathway. Furthermore, the risk T allele of rs2251795 (3q26.2) was associated with longer telomere length in both normal and tumour tissues. Our findings elucidated the significance of genetic factors in the pathogenesis of leiomyoma.