TY - JOUR
T1 - Identification of a novel uterine leiomyoma GWAS locus in a Japanese population
AU - Sakai, Kensuke
AU - Tanikawa, Chizu
AU - Hirasawa, Akira
AU - Chiyoda, Tatsuyuki
AU - Yamagami, Wataru
AU - Kataoka, Fumio
AU - Susumu, Nobuyuki
AU - Terao, Chikashi
AU - Kamatani, Yoichiro
AU - Takahashi, Atsushi
AU - Momozawa, Yukihide
AU - Hirata, Makoto
AU - Kubo, Michiaki
AU - Fuse, Nobuo
AU - Takai-Igarashi, Takako
AU - Shimizu, Atsushi
AU - Fukushima, Akimune
AU - Kadota, Aya
AU - Arisawa, Kokichi
AU - Ikezaki, Hiroaki
AU - Wakai, Kenji
AU - Yamaji, Taiki
AU - Sawada, Norie
AU - Iwasaki, Motoki
AU - Tsugane, Shoichiro
AU - Aoki, Daisuke
AU - Matsuda, Koichi
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85078350407
UR - https://www.scopus.com/pages/publications/85078350407#tab=citedBy
U2 - 10.1038/s41598-020-58066-8
DO - 10.1038/s41598-020-58066-8
M3 - Article
C2 - 31988393
AN - SCOPUS:85078350407
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 1197
ER -