{"id":"hum0014","version":24,"url":"https://humandbs.dbcls.jp/research/hum0014/v24","datePublished":"2021-11-26","versions":[{"version":1,"datePublished":"2014-09-30"},{"version":2,"datePublished":"2015-12-28"},{"version":3,"datePublished":"2016-01-28"},{"version":4,"datePublished":"2016-02-02"},{"version":5,"datePublished":"2017-05-18"},{"version":6,"datePublished":"2017-09-08"},{"version":7,"datePublished":"2018-04-04"},{"version":8,"datePublished":"2018-05-01"},{"version":9,"datePublished":"2018-08-07"},{"version":10,"datePublished":"2018-08-13"},{"version":11,"datePublished":"2018-10-16"},{"version":12,"datePublished":"2018-12-10"},{"version":13,"datePublished":"2019-01-25"},{"version":14,"datePublished":"2019-03-26"},{"version":15,"datePublished":"2019-09-27"},{"version":16,"datePublished":"2019-10-07"},{"version":17,"datePublished":"2019-10-08"},{"version":18,"datePublished":"2019-11-26"},{"version":19,"datePublished":"2020-04-20"},{"version":20,"datePublished":"2020-08-17"},{"version":21,"datePublished":"2020-08-25"},{"version":22,"datePublished":"2021-05-21"},{"version":23,"datePublished":"2021-07-13"},{"version":24,"datePublished":"2021-11-26"},{"version":25,"datePublished":"2022-01-25"},{"version":26,"datePublished":"2022-04-01"},{"version":27,"datePublished":"2022-12-31"},{"version":28,"datePublished":"2023-04-05"},{"version":29,"datePublished":"2023-04-05"},{"version":30,"datePublished":"2023-04-20"},{"version":31,"datePublished":"2023-09-01"},{"version":32,"datePublished":"2024-01-11"},{"version":33,"datePublished":"2024-05-27"},{"version":34,"datePublished":"2024-09-19"},{"version":35,"datePublished":"2024-10-25"},{"version":36,"datePublished":"2024-11-28"},{"version":37,"datePublished":"2025-05-09"}],"title":{"ja":"オーダーメイド医療の実現プログラム","en":"Bio Bank Japan project"},"summary":{"aims":{"ja":"日本人における疾患関連遺伝子の特定、日本人における転移因子挿入多型の網羅的探索、日本人集団に特化したリファレンスパネルの開発","en":"Identify disease-related genes and mobile element variations in Japanese/Development for Japanese population-specific reference panels"},"methods":{"ja":"Human610-Quad BeadChip、HumanHap550v3 Genotyping BeadChip、HumanOmniExpress-12 BeadChip、HumanExome BeadChip、 OmniExpressExome Beadchip（Illumina社）、high-density oligonucleotide arrays （Perlegen Sciences社）、もしくはインベーダー法（Hologic Japan社）により遺伝子型を決定し、心筋梗塞、2型糖尿病、アトピー性皮膚炎、心房細動、Body Mass Index（BMI）、開放隅角緑内障、58形質、初潮・閉経年齢、喫煙習慣、身長、42疾患（4疾患は以前のリリースと一部重複あり）、食習慣、および冠動脈疾患のゲノムワイド関連解析（Genome Wide Association Study：GWAS）や2型糖尿病腎症および2型糖尿病発症のGWASメタ解析を実施した。51疾患患者26.9万名のSNPアレイ解析を実施した。また、Illumina社 HiSeq 2500/X Fiveを用いて、BBJ第1コホート1,026＋1,007名、心筋梗塞1,765症例、認知症199症例、胃がん256＋2,067症例、大腸がん617症例、糖尿病2,162症例の全ゲノムシークエンス（Whole Genome Sequencing：WGS）を実施した。乳がん7,104症例と対照者23,731名における遺伝性乳がん原因11遺伝子翻訳領域、遺伝性前立腺がん7,636症例と対照者12,366名における遺伝性前立腺がん原因8遺伝子翻訳領域、バイオバンクジャパン11,234名における23遺伝子、膵がん1,005症例、大腸がん12,503症例および対照者23,705名、腎がん740症例および対照者5,996名、リンパ腫1,982症例、胃がん10,366症例および対照者37,592名の遺伝性腫瘍関連27遺伝子翻訳領域ならびに腎がん740症例および対照者5,996名の腎がん関連13遺伝子翻訳領域のTarget Capture Sequencingを実施した。また、乳がん10,008症例、胃がん10,576症例、大腸がん13,922症例および心不全6,038症例、脳梗塞10,486症例などを含む計140,597名に対してTP53のTarget Capture Sequencingを実施した。バイオバンクジャパン7,472名もしくは3,256名のWGSデータから作成したvcfファイルと1000ゲノムプロジェクト（Phase3v5）2,504名のvcfファイルを統合し、genotype imputation用reference panelを作成した。バイオバンクジャパン137,693名について、男女別にCox回帰分析を実施した。当研究室が開発したソフトウェアを用い、バイオバンクジャパンの第1コホート4,880名のWGSデータから転移因子多型の同定を行った。バイオバンクジャパンの心房細動ケース9,826人とコントロール140,446人で心房細動GWASを実施し、さらに欧米人の心房細動GWAS（http://csg.sph.umich.edu/willer/public/afib2018; 60,620人ケースと970,216人コントロール、FinnGen; https://www.finngen.fi/en; 7,244人ケースと56,378人コントロール）とメタ解析を行った。メタ解析の結果からポリジェニックリスクスコアを構築した。","en":"Genomic DNA samples were genotyped by following methods: Human610-Quad BeadChip, HumanHap550v3 Genotyping BeadChip, HumanOmniExpress-12 BeadChip, HumanExome BeadChip, OmniExpressExome BeadChip (Illumina), high-density oligonucleotide arrays (Perlegen Sciences), or Invader (Hologic Japan). Genome-Wide Association Studies (GWAS) for myocardial infarction (MI) , type II diabetes mellitus (T2DM), Atopic dermatitis (AD), atrial fibrillation (AF), Body Mass Index (BMI), primary open-angle glaucoma (POAG), 58 quantitative traits, age at menarche / menopause, smoking behaviour, height, 42 diseases (among them, the samples of 4 diseases were partially overlapped with those of previous release), dietary habits, and coronary artery disease were performed using about 500-2700K variants. Meta analyses for T2DM with diabetic nephropathy and for T2DM were also performed. SNP array analysis for 51 diseases registered in Biobank Japan were performed. Whole-genome sequencing analyses for 1,026 + 1,007 patients, who were registered Bio Bank Japan from 2003 - 2007, 1,765 myocardial infarction patients, 199 dementia patients, 256 + 2,067 gastric cancer patients, 617 colorectal cancer patients and 2,162 diabetes patients were performed with Illumina HiSeq 2500/X Five. Target sequencing analyses of 11 hereditary breast cancer genes in 7,104 breast cancer patients and 23,731 controls, 8 hereditary prostate cancer genes in 7,636 prostate cancer patients and 12,366 controls, 23 genes related to clonal hematopoiesis in 11,234 subjects extracted from approximately 200,000 subjects registered in Biobank Japan between fiscal years 2003 to 2007, 27 cancer-predisposing genes in 1,009 pancreatic cancer patients, 12,606 colorectal cancer patients, 740 renal cell cancer patients, 1,982 lymphoma patients, 10,366 gastric cancer patients and 23,780 + 5,996 + 37,592 controls and 13 renal cell carcinoma-related genes in 740 renal cell cancer patients and 5,996 controls were performed with Illumina HiSeq 2500. Also targeted sequencing was performed on the coding regions of TP53 in 140,597 individuals, including those with breast cancer, stomach cancer, colon cancer, heart failure, stroke, etc. SNP array analysis for 11,234 subjects was performed. A new reference panel was build with WGS data of the biobank Japan project (N=7,472 or 3,256) and the 1KGPp3v5 ALL (N=2,504). Sex-stratified genome-wide association studies using a Cox proportional hazard model under the assumption of the additive genetic model were performed. Associations of genetic variants estimated by saddle point estimation using SPACox software were also evaluated. A mobile element variation (MEV) search tool, MEGAnE, was applied to 4,880 WGS conducted in BBJ and 24,933 MEVs were found. Genome-wide association study for atrial fibrillation was performed in 9,826 cases and 140,446 controls. A subsequent cross-ancestry meta-analysis with European GWAS (60,620 cases and 970,216 controls; http://csg.sph.umich.edu/willer/public/afib2018) and Finnish GWAS (7,244 cases and 56,378 controls; FinnGenn; https://www.finngen.fi/en) was performed (77,690 cases and 1,167,040 controls in total). Polygenic risk score was constructed based on the cross-ancestry meta-analysis of atrial fibrillation."},"targets":{"ja":"オーダーメイド医療実現化プロジェクトおよびオーダーメイド医療の実現プログラム参加者","en":"Participants for the Tailor-made Medical Treatment Program (BioBank Japan: BBJ)"},"url":{"ja":[{"url":"https://biobankjp.org/index.html","text":"https://biobankjp.org/index.html"}],"en":[{"url":"https://biobankjp.org/en","text":"https://biobankjp.org/en"}]}},"listingSummary":{},"releaseNote":{"ja":"Illumina社のHiSeq 2500を使用して取得した、膵がん1,005症例、大腸がん12,503症例および対照者23,705名の遺伝性腫瘍関連27遺伝子翻訳領域のターゲットシークエンスデータを追加した（fastq）。","en":"A target capture sequencing analysis of 27 cancer-predisposing genes in 1,005 pancreatic cancer patients, 12,503 colorectal cancer patients and 23,705 controls was performed. Fastq files are provided."},"dataProviders":[{"name":{"ja":"久保 充明","en":"Michiaki Kubo"},"organization":{"name":{"ja":"理化学研究所 統合生命医科学研究センター 疾患多様性医科学研究部門","en":"RIKEN Center for Integrative Medical Sciences"}}}],"researchProjects":[{"name":{"ja":"オーダーメイド医療の実現プログラム","en":"Tailor-made Medical Treatment Program (Bio Bank Japan: BBJ)"},"url":{"ja":[{"url":"https://biobankjp.org/index.html","text":"https://biobankjp.org/index.html"}],"en":[{"url":"https://biobankjp.org/en","text":"https://biobankjp.org/en"}]}}],"grants":[{"title":{"ja":"加齢や炎症に伴う組織の再構築と機能低下","en":"Research on altered tissue functions caused by clonal expansion and remodeling of apparently normal tissues related to normal aging or exposure to chronic inflammation and other lifestyles"},"agency":{"ja":"日本医療研究開発機構 革新的先端研究開発支援事業（AMED-CREST）","en":"Core Research and Evolutional Science and Technology, Advanced Research & Development Programs for Medical Innovation, Japan Agency for Medical Research and Development (AMED-CREST)"},"grantIds":["JP19gm1110011"]},{"title":{"ja":"先端ゲノミクスを駆使したがんの初期発生とクローン進化に関わる分子基盤の解明","en":"Comprehensive studies on the molecular basis of early development and clonal evolution in cancer using advanced genomics."},"agency":{"ja":"科学研究費助成事業 基盤研究（S）","en":"KAKENHI Grant-in-Aid for Scientific Research (S)"},"grantIds":["19H05656"]},{"title":{"ja":"乳がん・大腸がん・膵がんに対する適切な薬剤投与を可能にする大規模データ基盤の構築","en":"Development of a large-scale database for effective drug treatment for breast, colorectal, and pancreas cancers"},"agency":{"ja":"日本医療研究開発機構（AMED） 疾病克服に向けたゲノム医療実現プロジェクト ゲノム創薬基盤推進研究事業","en":"Program for Promoting Platform of Genomics based Drug Discovery, Project for Genome and Health Related Data, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP19kk0305010"]},{"title":{"ja":"転移因子の挿入多型と疾患とのゲノムワイド関連解析","en":"Genome-wide association study integrating mobile genetic elements"},"agency":{"ja":"科学研究費助成事業 若手研究","en":"KAKENHI Grant-in-Aid for Early-Career Scientists"},"grantIds":["22K15385"]},{"title":{"ja":"心不全発症の基盤となる心筋脆弱性を規定する遺伝要因の解明","en":"Elucidation of genetic factors that define myocardial vulnerability as a basis for the development of heart failure"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["21H02919"]},{"title":{"ja":"ゲノム免疫：内在性ウイルスの抗ウイルス活性の動作原理解明と機能資源としての確保","en":"Genome immunity: elucidation of the antiviral activity of endogenous bornaviruses and their utilization as functional resources"},"agency":{"ja":"科学研究費助成事業 基盤研究（S）","en":"KAKENHI Grant-in-Aid for Scientific Research (S)"},"grantIds":["20H05682"]},{"title":{"ja":"ヘルペスウイルスのゲノムへの組み込みと再活性化: 大規模解析から探る疾患との関連","en":"Integration and reactivation of human herpesvirus 6: association with diseases"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["21H02972"]},{"title":{"ja":"利活用を目的とした日本疾患バイオバンクの運営・管理","en":"Management of the Japanese biobank"},"agency":{"ja":"日本医療研究開発機構（AMED） ゲノム医療実現バイオバンク利活用プログラム（B-Cure）","en":"Biobank - Construction and Utilization biobank for genomic medicine REalization (B-Cure), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP19km0605001"]},{"title":{"ja":"心房細動・重篤合併症予防を実現する多層的・統合的エビデンス創出研究","en":"Multi-layered and integrated research for prevention of atrial fibrillation and serious complications"},"agency":{"ja":"日本医療研究開発機構（AMED） 循環器疾患・糖尿病等生活習慣病対策実用化研究事業","en":"Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP22ek0210164"]},{"title":{"ja":"全ゲノム解析と組織オミックス解析による心房細動の病態解明と精密医療","en":"Understanding pathogenesis of atrial fibrillation and implementation of precision medicine by WGS and multi-omics"},"agency":{"ja":"日本医療研究開発機構（AMED） ゲノム医療実現バイオバンク利活用プログラム","en":"Biobank - Construction and Utilization biobank for genomic medicine REalization, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP21tm0724601"]},{"title":{"ja":"マルチオミックス連関による循環器疾患における次世代型精密医療の実現","en":"Implementation of next-generation precision medicine for cardiovascular disease by multi-omics"},"agency":{"ja":"日本医療研究開発機構（AMED） ゲノム医療実現バイオバンク利活用プログラム","en":"Biobank - Construction and Utilization biobank for genomic medicine REalization, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP20km0405209"]},{"title":{"ja":"難治性心血管疾患におけるマルチオミックス解析による病態解明と精密医療","en":"Understanding pathology and implementation of precision medicine for intractable cardiovascular disease by multi-omics analysis"},"agency":{"ja":"日本医療研究開発機構（AMED） 難治性疾患実用化研究事業","en":"Practical Research Project for Rare / Intractable Diseases, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP20ek0109487"]},{"title":{"ja":"生体試料を用いた大規模機能ゲノミクス解析支援及びヒト免疫機能評価基盤の高度化","en":"Support for large-scale functional genomics and development for the platform of evaluating functions of human immunological systems"},"agency":{"ja":"日本医療研究開発機構（AMED） 生命科学・創薬研究支援基盤事業","en":"Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP22ama121015"]},{"title":{"ja":"23がん種14万人を用いた遺伝・環境・生活習慣を統合した各個人の疾患リスクの推定","en":"Risk estimation of each cancer risk by integrating genetic, environmental, and lifestyle factors in 140,000 samples of 23 cancer types"},"agency":{"ja":"日本医療研究開発機構（AMED） 革新的がん医療実用化研究事業","en":"Practical Research for Innovative Cancer Control, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP23ck0106805"]},{"title":{"ja":"利活用を目的とした日本疾患バイオバンクの運営・管理","en":"Management of the Japanese biobank"},"agency":{"ja":"日本医療研究開発機構（AMED） ゲノム研究バイオバンク事業","en":"BioBank Japan Project for Genomic and Clinical Research, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP23tm0624002"]},{"title":{"ja":"オーダーメイド医療の実現プログラム（第3期）","en":"Tailor-made Medical Treatment Program (the 3rd phase)"},"agency":{"ja":"文部科学省 科学技術試験研究委託事業費","en":"Ministry of Education, Culture, Sports, Science and Technology in Japan"},"grantIds":null},{"title":{"ja":"疾患関連遺伝子等の探索を効率化するための遺伝子多型情報の高度化","en":"Generating large-scale data of genetic polymorphism to identify disease-related genes"},"agency":{"ja":"日本医療研究開発機構（AMED） オーダーメイド医療の実現プログラム","en":"Tailor-Made Medical Treatment with the BioBank Japan Project (BBJ), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP17km0305002"]},{"title":{"ja":"大規模シーケンス解析に基づく、造血器腫瘍のゲノム、エピゲノムにおける、空間的・時間的多様性の研究","en":"Exploration of special and temporal diversity in genome and epigenome of hematological malignancies based on large-scale sequencing analyses."},"agency":{"ja":"日本医療研究開発機構（AMED） 次世代がん医療創生研究事業（P-CREATE）","en":"Project for Cancer Research and Therapeutic Evolution (P-CREATE), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP19cm0106501"]}],"relatedPublications":[{"title":"A genome-wide association study identifies PLCL2 and AP3D1-DOT1L-SF3A2 as new susceptibility loci for myocardial infarction in Japanese.","doi":"https://doi.org/10.1038/ejhg.2014.110","datasets":["NHA000001"]},{"title":"A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese.","doi":"https://doi.org/10.1093/hmg/ddr268","datasets":["NHA000007"]},{"title":"Functional variants in ADH1B and ALDH2 coupled with alcohol and smoking synergistically enhance esophageal cancer risk.","doi":"https://doi.org/10.1053/j.gastro.2009.07.070","datasets":["NHA000006"]},{"title":"SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations.","doi":"https://doi.org/10.1038/ng.208","datasets":["NHA000021"]},{"title":"Common variants in a novel gene, FONG on chromosome 2q33.1 confer risk of osteoporosis in Japanese.","doi":"https://doi.org/10.1371/journal.pone.0019641","datasets":["NHA000034"]},{"title":"Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.","doi":"https://doi.org/10.1038/ncomms10531","datasets":["NHA000044","NHA000045"]},{"title":"Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis.","doi":"https://doi.org/10.1038/ng.3424","datasets":["NHA000046"]},{"title":"Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population.","doi":"https://doi.org/10.1038/ng.2438","datasets":["NHA000046"]},{"title":"Identification of six new genetic loci associated with atrial fibrillation in the Japanese population.","doi":"https://doi.org/10.1038/ng.3842","datasets":["NHA000052"]},{"title":"Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.","doi":"https://doi.org/10.1038/ng.3951","datasets":["NHA000053","JGAD000123","JGAD000124"]},{"title":"Genome-wide association study identifies seven novel susceptibility loci for primary open-angle glaucoma.","doi":"https://doi.org/10.1093/hmg/ddy053","datasets":["NHA000068"]},{"title":"Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.","doi":"https://doi.org/10.1038/s41588-018-0047-6","datasets":["NHA000070","JGAD000144","JGAD000145","JGAD000146","JGAD000147","JGAD000148","JGAD000149","JGAD000150","JGAD000151","JGAD000152","JGAD000153","JGAD000154","JGAD000155","JGAD000156","JGAD000157","JGAD000158","JGAD000159","JGAD000160","JGAD000161","JGAD000162","JGAD000163","JGAD000164","JGAD000165","JGAD000166","JGAD000167","JGAD000168","JGAD000169","JGAD000170","JGAD000171","JGAD000172","JGAD000173","JGAD000174","JGAD000175","JGAD000176","JGAD000177","JGAD000178","JGAD000179","JGAD000180","JGAD000181","JGAD000182","JGAD000183","JGAD000184","JGAD000185","JGAD000186","JGAD000187","JGAD000188","JGAD000189","JGAD000190","JGAD000191","JGAD000192","JGAD000193","JGAD000194","JGAD000195","JGAD000196","JGAD000197","JGAD000198","JGAD000199","JGAD000200","JGAD000201"]},{"title":"Elucidating the genetic architecture of reproductive ageing in the Japanese population","doi":"https://doi.org/10.1038/s41467-018-04398-z","datasets":["NHA000073","NHA000072"]},{"title":"Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese.","doi":"https://doi.org/10.1038/s41467-018-03274-0","datasets":["JGAD000220"]},{"title":"Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.","doi":"https://doi.org/10.1038/s41467-018-06581-8","datasets":["JGAD000209"]},{"title":"A Variant within the FTO confers susceptibility to diabetic nephropathy in Japanese patients with type 2 diabetes","doi":"https://doi.org/10.1371/journal.pone.0208654","datasets":["NHA000075"]},{"title":"Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population","doi":"https://doi.org/10.1038/s41588-018-0332-4","datasets":["NHA000078"]},{"title":"GWAS of smoking behaviour in 165,436 Japanese people reveals seven new loci and shared genetic architecture.","doi":"https://doi.org/10.1038/s41562-019-0557-y","datasets":["NHA000080","NHA000081","NHA000082","NHA000083"]},{"title":"Characterizing rare and low-frequency height-associated variants in the Japanese population","doi":"https://doi.org/10.1038/s41467-019-12276-5","datasets":["JGAD000220","NHA000088","JGAD000777"]},{"title":"Germline pathogenic variants in 7,636 Japanese patients with prostate cancer and 12,366 controls.","doi":"https://doi.org/10.1093/jnci/djz124","datasets":["JGAD000288"]},{"title":"Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different 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