Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population

Sosuke Adachi, Adachi S, Atsushi Tajima, Jinhua Quan, Quan J, Haino K, Kazufumi Haino, Kosuke Yoshihara, Hideaki Masuzaki, Masuzaki H, Hidetaka Katabuchi, Katabuchi H, Ikuma K, Kenichiro Ikuma, Suginami H, H. Suginami, Hiroshi Suginami, Nao Nishida, Nishida N, Ryozo Kuwano, Kuwano R, Yuji Okazaki, Okazaki Y, Yoshiya Kawamura, Kawamura Y, Takehiko Sasaki, Sasaki T, Tsukasa Sasaki, Katsushi Tokunaga, Tokunaga K, Inoue I, Ituro Inoue, Tanaka K, Kenichi Tanaka
Journal of human genetics · 2010 · vol. 55(12) , pp. 816–821 · doi:10.1038/jhg.2010.118 · PMID:20844546 · W2049790971
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A meta-analysis of Japanese genome-wide association studies found no common susceptibility locus for endometriosis but observed an excess of SNPs near IL1A.

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This paper performed a meta-analysis of two genome-wide association scans in Japanese women to identify genetic susceptibility loci for endometriosis, using case–control cohorts genotyped on Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0 and applying stringent quality control. After combining new genotype data with previously analyzed Japanese data, the analysis tested 282,838 SNPs for association using 696 endometriosis patients and 825 controls. The meta-analysis found no clear common susceptibility locus with a large effect, but detected an excess of SNPs with P<10−4, and among the top signals (P<10−5) four of five SNPs were located in or around IL1A, suggesting it as a possible functional candidate. The authors note that larger case–control cohorts are needed to clarify genetic risk factors, and this paper is centrally about endometriosis — identifying IL1A-proximal genetic signals in a Japanese GWAS meta-analysis.

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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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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. Similar content being viewed by others Log in or create a free account to read this content Gain free access to this article, as well as selected content from this journal and more on nature.com or

References

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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). Author information Authors and Affiliations Corresponding authors Additional information Supplementary Information accompanies the paper on Journal of Human Genetics website Rights and permissions About this article Cite this article 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 Received: Revised: Accepted: Published: Issue date: DOI: https://doi.org/10.1038/jhg.2010.118

Keywords

This article is cited by - APOBEC mediated mutagenesis drives genomic heterogeneity in endometriosis Journal of Human Genetics (2022) - Integration of genome-wide association study and expression quantitative trait locus mapping for identification of endometriosis-associated genes Scientific Reports (2021) - Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs Scientific Reports (2018) - The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis Molecular Genetics and Genomics (2018) - A higher prevalence of endometriosis among Asian women does not contribute to poorer IVF outcomes Journal of Assisted Reproduction and Genetics (2017)

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endometriosis

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Endometriosis Genetic Predisposition to Disease Genome-Wide Association Study Adult Asian People Asian People Cohort Studies Endometriosis Female Humans Interleukin-1alpha Interleukin-1alpha Polymorphism, Single Nucleotide

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