A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese

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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 × 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 × 10−6, odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.

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Figure 1: P value plots, genomic structures and LD maps of chromosome 9p21.


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We thank the members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. We also thank the technical staff of the Laboratory for Genotyping Development in RIKEN, Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo and Department of Obstetrics and Gynecology, Keio University, School of Medicine. This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government.

Author information

Y.N. conceived the study. Y.N., H.Z., S.U., K.H. and M.K. designed the study. S.U., T.A. and M.K. performed genotyping. S.U., A.T., N.K. and M.K. performed the data analyses. Y.N., H.Z., and M.K. managed DNA samples belonging to BioBank Japan. A.H. and D.A. managed DNA samples belonging to Keio University. S.U. summarized the results. S.U., H.Z. and Y.N. wrote the manuscript. Y.N. obtained funding for the study.

Correspondence to Yusuke Nakamura.

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