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A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids

Abstract

Uterine fibroids are a common benign tumor of the female genital tract. We conducted a genome-wide association study in which 457,044 SNPs were analyzed in 1,607 individuals with clinically diagnosed uterine fibroids and 1,428 female controls. SNPs showing suggestive associations (P < 5 × 10−5) were further genotyped in 3,466 additional cases and 3,245 female controls. Three loci on chromosomes 10q24.33, 22q13.1 and 11p15.5 revealed genome-wide significant associations with uterine fibroids. The SNPs showing the most significant association in a combination analysis at each of these loci were rs7913069 (P = 8.65 × 10−14, odds ratio (OR) = 1.47), rs12484776 (P = 2.79 × 10−12, OR = 1.23) and rs2280543 (P = 3.82 × 10−12, OR = 1.39), respectively. Subsequent fine mapping of these regions will be necessary to pinpoint the causal variants. Our findings should shed light on the pathogenesis of uterine fibroids.

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Figure 1
Figure 2: Regional association plots and recombination rates of the three loci associated with uterine fibroids at chromosomes 10q24.33 (SLK and OBFC1) (a), 22q13.1 (TNCRB6) (b) and 11p15.5 (ODF3-BET1L-RIC8A-SIRT3) (c).

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Acknowledgements

We extend our heartfelt gratitude to all subjects who kindly participated in the current study. We also thank the BioBank Japan for providing DNA samples and clinical information. Finally, we acknowledge members of the Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, for their excellent technical assistance. This work was supported by Leading Project for Personalized Medicine in the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

Authors

Contributions

Y.N. initiated the recruitment of samples, obtained financial support and conceived the study. Y.N., M.K. and P.-C.C. designed the study. P.-C.C. performed SNP selection, genotyping, data analysis and prepared the manuscript. A.T. performed quality assessment and statistical analysis of GWAS data. M.K. and N.H. supervised and conducted the GWAS. S.-K.L. helped with preparation of figures. N.K. supervised the statistical analysis. M.K. and Y.N. critically reviewed and edited the manuscript.

Corresponding author

Correspondence to Yusuke Nakamura.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Table 1 and Supplementary Figures 1–7. (PDF 852 kb)

Supplementary Table 2

Associations of the 46 SNPs examined in GWAS, replication study, and combined analysis (XLS 78 kb)

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Cha, PC., Takahashi, A., Hosono, N. et al. A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nat Genet 43, 447–450 (2011). https://doi.org/10.1038/ng.805

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