Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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).


  1. Stewart, E.A. Uterine fibroids. Lancet 357, 293–298 (2001).

    Article  CAS  Google Scholar 

  2. Buttram, V.C. Jr. & Reiter, R.C. Uterine leiomyomata: etiology, symptomatology, and management. Fertil. Steril. 36, 433–445 (1981).

    Article  Google Scholar 

  3. Flake, G.P., Andersen, J. & Dixon, D. Etiology and pathogenesis of uterine leiomyomas: a review. Environ. Health Perspect. 111, 1037–1054 (2003).

    Article  CAS  Google Scholar 

  4. Sozen, I. & Arici, A. Interactions of cytokines, growth factors, and the extracellular matrix in the cellular biology of uterine leiomyomata. Fertil. Steril. 78, 1–12 (2002).

    Article  Google Scholar 

  5. Parazzini, F. et al. Reproductive factors and risk of uterine fibroids. Epidemiology 7, 440–442 (1996).

    Article  CAS  Google Scholar 

  6. Marsh, E.E. et al. Differential expression of microRNA species in human uterine leiomyoma versus normal myometrium. Fertil. Steril. 89, 1771–1776 (2008).

    Article  CAS  Google Scholar 

  7. Bonatz, G. et al. Telomere shortening in uterine leiomyomas. Am. J. Obstet. Gynecol. 179, 591–596 (1998).

    Article  CAS  Google Scholar 

  8. Malik, M., Norian, J., McCarthy-Keith, D., Britten, J. & Catherino, W.H. Why leiomyomas are called fibroids: the central role of extracellular matrix in symptomatic women. Semin. Reprod. Med. 28, 169–179 (2010).

    Article  Google Scholar 

  9. El-Gharib, M.N. & Elsobky, E.S. Cytogenetic aberrations and the development of uterine leiomyomata. J. Obstet. Gynaecol. Res. 36, 101–107 (2010).

    Article  Google Scholar 

  10. Treloar, S.A., Martin, N.G., Dennerstein, L., Raphael, B. & Heath, A.C. Pathways to hysterectomy: insights from longitudinal twin research. Am. J. Obstet. Gynecol. 167, 82–88 (1992).

    Article  CAS  Google Scholar 

  11. Vikhlyaeva, E.M., Khodzhaeva, Z.S. & Fantschenko, N.D. Familial predisposition to uterine leiomyomas. Int. J. Gynaecol. Obstet. 51, 127–131 (1995).

    Article  CAS  Google Scholar 

  12. Storbeck, C.J. et al. Ste20-like kinase SLK displays myofiber type specificity and is involved in C2C12 myoblast differentiation. Muscle Nerve 29, 553–564 (2004).

    Article  CAS  Google Scholar 

  13. Wagner, S. et al. FAK/src-family dependent activation of the Ste20-like kinase SLK is required for microtubule-dependent focal adhesion turnover and cell migration. PLoS One 3, e1868 (2008).

    Article  Google Scholar 

  14. Levy, D. et al. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc. Natl. Acad. Sci. USA 107, 9293–9298 (2010).

    Article  CAS  Google Scholar 

  15. Meister, G. et al. Identification of novel argonaute-associated proteins. Curr. Biol. 15, 2149–2155 (2005).

    Article  CAS  Google Scholar 

  16. Luo, X. & Chegini, N. The expression and potential regulatory function of microRNAs in the pathogenesis of leiomyoma. Semin. Reprod. Med. 26, 500–514 (2008).

    Article  CAS  Google Scholar 

  17. Egydio de Carvalho, C. et al. Molecular cloning and characterization of a complementary DNA encoding sperm tail protein SHIPPO 1. Biol. Reprod. 66, 785–795 (2002).

    Article  CAS  Google Scholar 

  18. Xu, Y., Martin, S., James, D.E. & Hong, W. GS15 forms a SNARE complex with syntaxin 5, GS28, and Ykt6 and is implicated in traffic in the early cisternae of the Golgi apparatus. Mol. Biol. Cell 13, 3493–3507 (2002).

    Article  CAS  Google Scholar 

  19. Thomas, C.J., Tall, G.G., Adhikari, A. & Sprang, S.R. Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3. J. Biol. Chem. 283, 23150–23160 (2008).

    Article  CAS  Google Scholar 

  20. Kim, H.S. et al. SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 17, 41–52 (2010).

    Article  CAS  Google Scholar 

  21. Ohnishi, Y. et al. A high-throughput SNP typing system for genome-wide association studies. J. Hum. Genet. 46, 471–477 (2001).

    Article  CAS  Google Scholar 

  22. Stranger, B.E. et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 315, 848–853 (2007).

    Article  CAS  Google Scholar 

  23. Heinzen, E.L. et al. Tissue-specific genetic control of splicing: implications for the study of complex traits. PLoS Biol. 6, e1 (2008).

    Article  Google Scholar 

  24. International HapMap Consortium. The International HapMap Project. Nature 426, 789–796 (2003).

Download references


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.

Author information

Authors and Affiliations



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.

Ethics declarations

Competing interests

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)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer