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

Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi Hirata, Yusuke Nakamura

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)707-710
Number of pages4
JournalNature Genetics
Volume42
Issue number8
DOIs
Publication statusPublished - Aug 1 2010
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Endometriosis
Single Nucleotide Polymorphism
Cyclin-Dependent Kinase Inhibitor p15
Chromosomes
Odds Ratio
Antisense RNA
Introns

ASJC Scopus subject areas

  • Genetics

Cite this

A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. / Uno, Satoko; Zembutsu, Hitoshi; Hirasawa, Akira; Takahashi, Atsushi; Kubo, Michiaki; Akahane, Tomoko; Aoki, Daisuke; Kamatani, Naoyuki; Hirata, Koichi; Nakamura, Yusuke.

In: Nature Genetics, Vol. 42, No. 8, 01.08.2010, p. 707-710.

Research output: Contribution to journalArticle

Uno, S, Zembutsu, H, Hirasawa, A, Takahashi, A, Kubo, M, Akahane, T, Aoki, D, Kamatani, N, Hirata, K & Nakamura, Y 2010, 'A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese', Nature Genetics, vol. 42, no. 8, pp. 707-710. https://doi.org/10.1038/ng.612
Uno, Satoko ; Zembutsu, Hitoshi ; Hirasawa, Akira ; Takahashi, Atsushi ; Kubo, Michiaki ; Akahane, Tomoko ; Aoki, Daisuke ; Kamatani, Naoyuki ; Hirata, Koichi ; Nakamura, Yusuke. / A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. In: Nature Genetics. 2010 ; Vol. 42, No. 8. pp. 707-710.
@article{1f0b1adc7f9d4ad99b34fccbdd0a9963,
title = "A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese",
abstract = "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.",
author = "Satoko Uno and Hitoshi Zembutsu and Akira Hirasawa and Atsushi Takahashi and Michiaki Kubo and Tomoko Akahane and Daisuke Aoki and Naoyuki Kamatani and Koichi Hirata and Yusuke Nakamura",
year = "2010",
month = "8",
day = "1",
doi = "10.1038/ng.612",
language = "English",
volume = "42",
pages = "707--710",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese

AU - Uno, Satoko

AU - Zembutsu, Hitoshi

AU - Hirasawa, Akira

AU - Takahashi, Atsushi

AU - Kubo, Michiaki

AU - Akahane, Tomoko

AU - Aoki, Daisuke

AU - Kamatani, Naoyuki

AU - Hirata, Koichi

AU - Nakamura, Yusuke

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77955087088&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955087088&partnerID=8YFLogxK

U2 - 10.1038/ng.612

DO - 10.1038/ng.612

M3 - Article

C2 - 20601957

AN - SCOPUS:77955087088

VL - 42

SP - 707

EP - 710

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 8

ER -