Presentation Information
[O3-3]自己免疫疾患とアレルギー疾患を横断的に検討した多形質ゲノムワイド関連解析
○白井 雄也1,2, 中西 由光2,3,4, 鈴木 亜香里5, 小中 八郎6, 西川 里香7, 曽根原 究人1, 難波 真一1, 田中 宏明1,8, 増田 達郎9,10, 矢賀 元2, 佐藤 真吾2, 泉 真祐子2, 水野 裕美子2, 徐 立恒2, 前田 悠一2,3,11, 新居 卓朗2,11,12, 猪頭 英里2,11, バイオバンクジャパンプロジェクト13, 森崎 隆幸14,15, 鎌谷 洋一郎19, 中山田 真吾8, 錦織 千佳子7, 田中 良哉8, 武田 吉人2, 山本 一彦5, 熊ノ郷 淳2, 岡田 随象1,16,17,18 (1.大阪大学大学院医学系研究科 遺伝統計学, 2.大阪大学大学院医学系研究科 呼吸器・免疫内科学, 3.大阪大学免疫学フロンティア研究センター 感染病態分野, 4.大阪大学大学院医学系研究科 先端免疫臨床応用学共同研究講座, 5.理化学研究所生命医科学研究センター 自己免疫疾患研究チーム, 6.日本生命病院 呼吸器・免疫内科, 7.神戸大学大学院医学系研究科 内科系講座皮膚科学教室, 8.産業医科大学医学部 第一内科学講座, 9.大阪大学大学院医学系研究科 産婦人科学, 10.大阪大学大学院医学系研究科保健学専攻 再生誘導医学協働研究所, 11.大阪大学大学院医学系研究科 免疫制御学, 12.国立病院機構大阪刀根山医療センター 呼吸器内科, 13.東京大学医科学研究所 バイオバンク・ジャパン, 14.東京大学医科学研究所 癌・細胞増殖部門 人癌病因遺伝子分野, 15.東京大学医学部附属病院 内科診療部門, 16.理化学研究所生命医科学研究センター システム遺伝学チーム, 17.大阪大学免疫学フロンティア研究センター 免疫統計学, 18.東京大学大学院医学系研究科 遺伝情報学, 19.東京大学大学院新領域創成科学研究科 メディカル情報生命専攻 複雑形質ゲノム解析分野)
【Objectives】 Autoimmune and allergic diseases are outcomes of immune system dysregulation. We aimed to elucidate different or shared genetic components between them.
【Methods】We estimated genetic correlation and performed multi-trait genome-wide association study meta-analysis of six immune-related diseases: rheumatoid arthritis, Graves' disease, type 1 diabetes for autoimmune diseases, and asthma, atopic dermatitis, and pollinosis for allergic diseases. By integrating large-scale biobank resources (Biobank Japan and UK biobank), our study included 105,721 cases and 433,663 controls. Newly identified variants were evaluated in 21,778 cases and 712,767 controls for two additional autoimmune diseases: psoriasis and systemic lupus erythematosus.
【Results】Autoimmune and allergic diseases were not classified based on genetic backgrounds, but they had multiple positive genetic correlations. Multi-trait meta-analysis newly identified six allergic disease-associated loci. We identified four loci shared between the autoimmune and allergic diseases (rs10803431 at PRDM2, odds ratio[OR]=1.06, P=2.3×10-8, rs2053062 at G3BP1, OR=0.90, P=2.9×10-8, rs2210366 at HBS1L, OR=1.07, P=2.5×10-8 in Japanese and rs4529910 at POU2AF1, OR=0.96, P=1.9×10-10 across ancestries). Associations of rs10803431 and rs4529910 were confirmed at the additional autoimmune diseases. Enrichment analysis demonstrated link to T cells, natural killer cells, and various cytokine signals.
【Conclusion】Our analysis should elucidate complex pathogenesis shared components across autoimmune and allergic diseases.
【Methods】We estimated genetic correlation and performed multi-trait genome-wide association study meta-analysis of six immune-related diseases: rheumatoid arthritis, Graves' disease, type 1 diabetes for autoimmune diseases, and asthma, atopic dermatitis, and pollinosis for allergic diseases. By integrating large-scale biobank resources (Biobank Japan and UK biobank), our study included 105,721 cases and 433,663 controls. Newly identified variants were evaluated in 21,778 cases and 712,767 controls for two additional autoimmune diseases: psoriasis and systemic lupus erythematosus.
【Results】Autoimmune and allergic diseases were not classified based on genetic backgrounds, but they had multiple positive genetic correlations. Multi-trait meta-analysis newly identified six allergic disease-associated loci. We identified four loci shared between the autoimmune and allergic diseases (rs10803431 at PRDM2, odds ratio[OR]=1.06, P=2.3×10-8, rs2053062 at G3BP1, OR=0.90, P=2.9×10-8, rs2210366 at HBS1L, OR=1.07, P=2.5×10-8 in Japanese and rs4529910 at POU2AF1, OR=0.96, P=1.9×10-10 across ancestries). Associations of rs10803431 and rs4529910 were confirmed at the additional autoimmune diseases. Enrichment analysis demonstrated link to T cells, natural killer cells, and various cytokine signals.
【Conclusion】Our analysis should elucidate complex pathogenesis shared components across autoimmune and allergic diseases.