Abstract
To identify susceptibility genes for endometriosis in Japanese women, genome-wide association (GWA) analysis was performed using two case–control cohorts genotyped with the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. In each of the two array cohorts, stringent quality control (QC) filters were applied to newly obtained genotype data, together with previously analyzed data from the Japanese Integrated Database Project. After QC-based filtering of samples and single nucleotide polymorphisms (SNPs) in each cohort, 282 838 SNPs in both genotyping platforms were tested for association with endometriosis using a meta-analysis of the two GWA studies with 696 patients with endometriosis and 825 controls. The meta-analysis revealed that a common susceptibility locus conferring a large effect on the disease risk was unlikely. On the other hand, an excess of SNPs with P-values <10−4 (36 vs 28 SNPs expected by chance) was observed in the meta-analysis. Of note, four of the top five SNPs with P-values <10−5 were located in and around IL1A (interleukin 1α), which might be a functional candidate gene for endometriosis. Further studies with larger case–control cohorts will be necessary to elucidate the genetic risk factors.
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Acknowledgements
All women with endometriosis were registered at the Niigata University Hospital, the Nagasaki University Hospital, the Kumamoto University Hospital, the Takarazuka City Hospital, the National Hospital Organization Kyoto Medical Center, the Nagaoka Red Cross Hospital, the Kido Hospital, the Niigata Cancer Center Hospital, the Suibarago Hospital, the Joetsu General hospital, the Kaetsu Hospital, the Niigata Medical Center, the Muikamachi Hospital, the Toyama Red Cross Hospital and the Syonai Hospital. We thank Katsunori Kashima, Nobumichi Nishikawa, Naoki Fukui and Masayuki Yamaguchi for the management of DNA samples. We thank China Seki, Akemi Yukawa, Hiromi Kamura and Eriko Tokubo for their technical assistance. The data used for this research are partly available at the website of ‘DB Development for Medical Application from Disease Analysis (https://gwas.lifesciencedb.jp/index.html),’ which is a part of the ‘Integrated Database Project’ funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan. This work was supported, in part, by 2008 Research and Study Program of Tokai University Educational System General Research Organization (AT).
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Adachi, S., Tajima, A., Quan, J. et al. Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population. J Hum Genet 55, 816–821 (2010). https://doi.org/10.1038/jhg.2010.118
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DOI: https://doi.org/10.1038/jhg.2010.118
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