GWAS要約統計量に基づく高予測能疾患発症リスク予測システム

基于GWAS汇总统计的高度预测疾病风险预测系统

• 批准号: 21K10439
• 负责人: 成田 暁
• 金额: $ 1.5万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K10439/
• 关键词: ゲノムワイド関連解析; ポリジェニックリスクスコア

本研究は、ゲノムワイド関連解析（GWAS）の要約統計量をもとに、疾患発症リスク予測システムの基盤を確立することを目的としている。2022年度は、他の研究機関との共同研究として、提供された検体のゲノム多型タイピングやimputation（遺伝子型推定）を実施した。これらのデータは、東北大学東北メディカル・メガバンク機構が運営、管理するバイオバンクに蓄積され、疾患リスク予測システムの基盤確立に向けて二次利用される見通しである。一方で、東北メディカル・メガバンク計画（TMM）地域住民コホートのゲノムコホートデータを用いてGWASを実施し、国内外の研究機関が主催する共同研究の一環として、GWAS要約統計量の提供を行った。Global Lipids Genetics Consortiumとの共同研究では、メタGWASの要約統計量を、染色体上の位置や機能、遺伝子発現量などのデータと組み合わせた統合解析により、脂質レベルと生物学的に関連する遺伝子を集中的に同定できることが示された。さらに、疾患リスク予測手法についても、Ueki & Tamiya (2016)が開発したsmooth-threshold multivariate genetic prediction（STMGP）を、TMM地域住民コホートデータおよびUKバイオバンクデータに適用し、予測能が従来の手法を上回る傾向が得られたほか、外部のGWAS要約統計量を取り込むことによる予測能の向上についても検証を実施した。

The purpose of this study is to establish the basis for the analysis of GWAS offer statistics and disease prediction. In 2022, the joint research of other research institutions will be carried out to provide information on the application of genetic polymorphism. Tohoku University Tohoku University The Tohoku Regional Development Project (TMM) is a joint effort by local and international research organizations to implement GWAS and provide GWAS statistics. The Global Lipids Genetics Consortium's joint research on GWAS offers statistics, location and function on chromosomes, gene expression, and genetic association. Ueki & Tamiya (2016) on the development of smooth-threshold multivariate genetic prediction (STMGP), on the application of TMM to local residents, on the upward trend of predictive energy from incoming methods, on the implementation of external GWAS offer statistics.

项目成果

Helmholtz Zentrum Munchen(ドイツ)

慕尼黑亥姆霍兹中心（德国）

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

• DOI: 10.1186/s13059-022-02837-1
• 发表时间: 2022-12-27
• 期刊: Genome biology
• 影响因子: 12.3

A cross-population atlas of genetic associations for 220 human phenotypes

• DOI: 10.1038/s41588-021-00931-x
• 发表时间: 2021-09-30
• 期刊: NATURE GENETICS
• 影响因子: 30.8
• 作者: Sakaue, Saori;Kanai, Masahiro;Okada, Yukinori
• 通讯作者: Okada, Yukinori

The power of genetic diversity in genome-wide association studies of lipids.

• DOI: 10.1038/s41586-021-04064-3
• 发表时间: 2021-12
• 期刊: Nature
• 影响因子: 64.8
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• 通讯作者: Willer CJ

Genome-wide association study of the risk of chronic kidney disease and kidney-related traits in the Japanese population: J-Kidney-Biobank

• DOI: 10.1038/s10038-022-01094-1
• 发表时间: 2022-11
• 期刊: Journal of Human Genetics
• 影响因子: 3.5
• 作者: Y. Sugawara;Y. Hirakawa;H. Nagasu;A. Narita;A. Katayama;J. Wada;M. Shimizu;T. Wada;H. Kitamura;T. Nakano;H. Yokoi;M. Yanagita;S. Goto;I. Narita;S. Koshiba;G. Tamiya;M. Nangaku;Masayuki Yamamoto;N. Kashihara