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. 2020 Jan 27;10(1):1197.
doi: 10.1038/s41598-020-58066-8.

Identification of a Novel Uterine Leiomyoma GWAS Locus in a Japanese Population

Free PMC article

Identification of a Novel Uterine Leiomyoma GWAS Locus in a Japanese Population

Kensuke Sakai et al. Sci Rep. .
Free PMC article


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 = 6.12 × 10-25 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.

Conflict of interest statement

The authors declare no competing interests.


Figure 1
Figure 1
Study design of a GWAS of uterine leiomyoma. The meta-analysis comprised three stages.
Figure 2
Figure 2
Manhattan plot of the meta-analysis of GWAS screening stage 1 and screening stage 2. The red horizontal line represents the genome-wide significance threshold of P = 6.6 × 10−9.

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