A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese.
Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 x 10(-12), odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 x 10(-6), odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.
Uno
Satoko
S
Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Zembutsu
Hitoshi
H
Hirasawa
Akira
A
Takahashi
Atsushi
A
Kubo
Michiaki
M
Akahane
Tomoko
T
Aoki
Daisuke
D
Kamatani
Naoyuki
N
Hirata
Koichi
K
Nakamura
Yusuke
Y
D000328:Adult; D044466:Asian People / Q000235:genetics*; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics*; D004198:Disease Susceptibility; D004715:Endometriosis / Q000235:genetics; D005260:Female; D005796:Genes; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016372:RNA, Antisense / Q000235:genetics*
C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D016372:RNA, Antisense