リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Identification of a novel uterine leiomyoma GWAS locus in a Japanese population (本文)」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Identification of a novel uterine leiomyoma GWAS locus in a Japanese population (本文)

坂井, 健良 慶應義塾大学

2020.03.23

概要

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.

この論文で使われている画像

参考文献

1. Kawamura, S. et al. Prevalence of uterine myoma detected by ultrasound examination in the atomic bomb survivors. Radiat. Res. 147, 753–758 (1997).

2. Baird, D. D., Dunson, D. B., Hill, M. C., Cousins, D. & Schectman, J. M. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence. Am. J. Obstet. Gynecol. 188, 100–107 (2003).

3. Catherino, W. H., Parrott, E. & Segars, J. Proceedings from theNational Institute of Child Health and Human Development conference on the Uterine Fibroid Research Update Workshop. Fertil. Steril. 95, 9–12 (2011).

4. Gupta, S., Jose, J. & Manyonda, I. Clinical presentation of fibroids. Best Pract. Res. Clin. Obstet. Gynaecol. 22, 615–626 (2008).

5. Cardozo, E. R. et al. The estimated annual cost of uterine leiomyomata in the United States. Am. J. Obstet. Gynecol. 206, 211.e1–9 (2012).

6. Marsh, E. E. & Bulun, S. E. Steroid hormones and leiomyomas. Obstet. Gynecol. Clin. North Am. 33, 59–67 (2006).

7. Ishikawa, H. et al. Progesterone is essential for maintenance and growth of uterine leiomyoma. Endocrinology 151, 2433–2442 (2010).

8. Moore, A. B. et al. Association of race, age and body mass index with gross pathology of uterine fibroids. J. Reprod. Med. 53, 90–96 (2008).

9. Dragomir, A. D. et al. Potential risk factors associated with subtypes of uterine leiomyomata. Reprod. Sci. 17, 1029–1035 (2010).

10. Baird, D. D. & Dunson, D. B. Why is parity protective for uterine fibroids? Epidemiology 14, 247–250 (2003).

11. Laughlin, S. K., Hartmann, K. E. & Baird, D. D. Postpartum factors and natural fibroid regression. Am. J. Obstet. Gynecol. 204, 496. e1–6 (2011).

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

13. Hirata, M. et al. Cross-sectional analysis of BioBank Japan clinical data: A large cohort of 200,000 patients with 47 common diseases. J. Epidemiol. 27, S9–S21 (2017).

14. Rafnar, T. et al. Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone- related traits. Nat. Commun. 9, 3636 (2018).

15. Välimäki, N. et al. Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. Elife 7, (2018).

16. Edwards, T. L. et al. A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids. Front. Genet. 10, 511 (2019).

17. Gallagher, C. S. et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat. Commun. 10, 4857 (2019).

18. Cha, P.-C. et al. A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nat. Genet. 43, 447–450 (2011).

19. Hellwege, J. N. et al. A multi-stage genome-wide association study of uterine fibroids in African Americans. Hum. Genet. 136, 1363–1373 (2017).

20. Mäkinen, N. et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 334, 252–255 (2011).

21. Lehtonen, R. et al. Biallelic inactivation of fumarate hydratase (FH) occurs in nonsyndromic uterine leiomyomas but is rare in other tumors. Am. J. Pathol. 164, 17–22 (2004).

22. Fusco, A. & Fedele, M. Roles of HMGA proteins in cancer. Nat. Rev. Cancer 7, 899–910 (2007).

23. Akiyama, M. et al. Genome-wide association study identifies 112 new loci for body mass index in the Japanese population. Nat. Genet. 49, 1458–1467 (2017).

24. Freedman, M. L. et al. Assessing the impact of population stratification on genetic association studies. Nat. Genet. 36, 388–393 (2004).

25. Tanikawa, C. et al. Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population. J. Am. Soc. Nephrol. 30, 855–864 (2019).

26. Yang, J.-H. et al. Impact of submucous myoma on the severity of anemia. Fertil. Steril. 95, 1769–72.e1 (2011).

27. Edwards, T. L., Hartmann, K. E. & Velez Edwards, D. R. Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans. Hum. Genet. 132, 1361–1369 (2013).

28. Rogalla, P. et al. Telomere repeat fragment sizes do not limit the growth potential of uterine leiomyomas. Biochem. Biophys. Res. Commun. 211, 175–182 (1995).

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

30. Codd, V. et al. Identification of seven loci affecting mean telomere length and their association with disease. Nat. Genet. 45, 422–7, 427e1–2 (2013).

31. Liu, Y. et al. A genome-wide association study identifies a locus on TERT for mean telomere length in Han Chinese. PLoS One 9, e85043 (2014).

32. Warrington, N. M. et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat. Genet. 51, 804–814 (2019).

33. Ono, M. et al. Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc. Natl. Acad. Sci. USA 110, 17053–17058 (2013).

34. Ono, M. et al. Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth. Fertil. Steril. 101, 1441–1449 (2014).

35. Ono, M., Bulun, S. E. & Maruyama, T. Tissue-specific stem cells in the myometrium and tumor-initiating cells in leiomyoma. Biol. Reprod. 91, 149 (2014).

36. Zhang, G. et al. Genetic Associations with Gestational Duration and Spontaneous Preterm Birth. N. Engl. J. Med. 377, 1156–1167 (2017).

37. Lu, L. et al. Functional study of risk loci of stem cell-associated gene lin-28B and associations with disease survival outcomes in epithelial ovarian cancer. Carcinogenesis 33, 2119–2125 (2012).

38. Lu, L. et al. An insulin-like growth factor-II intronic variant affects local DNA conformation and ovarian cancer survival. Carcinogenesis 34, 2024–2030 (2013).

39. Codd, V. et al. Common variants near TERC are associated with mean telomere length. Nat. Genet. 42, 197–199 (2010).

40. Mangino, M. et al. Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Hum. Mol. Genet. 21, 5385–5394 (2012).

41. Pooley, K. A. et al. A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk. Hum. Mol. Genet. 22, 5056–5064 (2013).

42. Prescott, J. et al. Genome-wide association study of relative telomere length. PLoS One 6, e19635 (2011).

43. Dorajoo, R. et al. Loci for human leukocyte telomere length in the Singaporean Chinese population and trans-ethnic genetic studies. Nat. Commun. 10, 2491 (2019).

44. Baird, D. M. Variation at the TERT locus and predisposition for cancer. Expert Rev. Mol. Med. 12, e16 (2010).

45. Walsh, K. M. et al. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nat. Genet. 46, 731–735 (2014).

46. Nagai, A. et al. Overview of the BioBank Japan Project: Study design and profile. J. Epidemiol. 27, S2–S8 (2017).

47. Tsugane, S. & Sawada, N. The JPHC study: design and some findings on the typical Japanese diet. Jpn. J. Clin. Oncol. 44, 777–782 (2014).

48. Hamajima, N. & J-MICC Study Group. The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) to detect gene- environment interactions for cancer. Asian Pac. J. Cancer Prev. 8, 317–323 (2007).

49. Kuriyama, S. et al. The Tohoku Medical Megabank Project: Design and Mission. J. Epidemiol. 26, 493–511 (2016).

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

51. International HapMap 3. Consortium et al. Integrating common and rare genetic variation in diverse human populations. Nature 467, 52–58 (2010).

52. Li, Y., Willer, C. J., Ding, J., Scheet, P. & Abecasis, G. R. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet. Epidemiol. 34, 816–834 (2010).

53. 1000 Genomes Project. Consortium et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).

54. Breslow, N. E. & Day, N. E. Statistical methods in cancer research. Volume II–The design and analysis of cohort studies. IARC Sci. Publ. 1–406 (1987).

55. Yang, J. et al. Genomic inflation factors under polygenic inheritance. Eur. J. Hum. Genet. 19, 807–812 (2011).

56. Pruim, R. J. et al. LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26, 2336–2337 (2010).

57. Tanikawa, C. et al. GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12. Carcinogenesis 39, 652–660 (2018).

58. Tanikawa, C. et al. Genome-wide association study identifies gastric cancer susceptibility loci at 12q24.11-12 and 20q11.21. Cancer Sci. 109, 4015–4024 (2018).

59. Kanai, M. et al. Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases. Nat. Genet. 50, 390–400 (2018).

60. Cawthon, R. M. Telomere measurement by quantitative PCR. Nucleic Acids Res. 30, e47 (2002).

参考文献をもっと見る