マルチスケール精神病データの疎性モデリング解析

• Project Area: Constructive understanding of multi-scale dynamism of neuropsychiatric disorders
• Project/Area Number: 19H05200
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: 田宮 元 東北大学, 医学系研究科, 教授 (10317745)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 疎性モデリング / 人工知能 / 機械学習 / ゲノムリスク予測 / ゲノムコホート / 高次元変数選択法 / 遺伝子×環境相互作用

Outline of Research at the Start

全相互作用効果の周辺回帰スクリーニングとそれに引き続く罰則回帰による変数選択を組み合わせた高次元変数選択の枠組み（SIS; Sure Independence Screening）ならびに、周辺回帰ランキング統計量を重みに用いたリッジ回帰の枠組みを、遺伝子×環境相互作用データの実データに適用可能となるよう拡張する。特に、各種コーディング法によるランキング統計量の分布について詳細な検証を行い、ソフトウェアの最適化を行う。

Outline of Annual Research Achievements

前年度に完成した遺伝子×遺伝子ならびに遺伝子×環境相互作用のための高次元変数選択法ソフトウェアについて、実際のゲノムコホートデータをテストデータとして適用し、この手法の妥当性を検証した。
具体的には、これまで作成してきた疎性モデリングのアルゴリズムを実装したソフトウェアプログラムを用いて、宮城県住民を対象とした東北メディカル・メガバンク機構の前向きゲノムコホートで取得されていた環境暴露データについて、各変数のコーディングを行った。次に、この前向きゲノムコホートで取得されていた100万程度のSNPsのジェノタイプデータを取り込みを行った。特に、SNPのクラスタリングエラーが相互作用検索時に深刻な偽陽性を生むことが知られているため、各SNPのクラスタリングに関するQCデータを利用し、低いクオリティのデータを事前に排除した。上記のデータをテストデータとして高次元変数選択法ソフトウェアにかけ、横断的な健康診断データを応答変数にして横断的解析を行い、次に、疾患二値データや前向きデータへの適用を試みた。さらに、うつ傾向スコア（CES-D）に適用して、ゲノムリスク予測を実施した。その結果、現在主流となっているPRS（ポリジェニックリスクスコア）の推定法であるP+Tなどの既存手法よりも高い予測性能を達成した。
このことは、ゲノムコホートからの精神健康状態に関するマルチスケールデータへ適用によって、遺伝子×遺伝子ならびに遺伝子×環境相互作用の解析が実行可能となり、リスク予測に有用である可能性を示している。この成果について、国際専門誌に論文発表を行った。

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study (2021)
  • Author(s): Hozawa A, Tanno K, Nakaya N, Nakamura T, Tsuchiya N, Hirata T, Narita A, Kogure M, Nochioka K, Sasaki R, Takanashi N, Otsuka K, Sakata K, Kuriyama S, Kikuya M, 13名略, Kobayashi T, 53名略, Yamamoto M.
  • Journal Title: Journal of Epidemiology Volume: 31 Issue: 1 Pages: 65-76
  • DOI: 10.2188/jea.JE20190271
  • NAID: 130007966030
  • ISSN: 0917-5040, 1349-9092
  • Year and Date: 2021-01-05
  • Peer Reviewed / Open Access
• [Journal Article] Construction and integration of three de novo Japanese human genome assemblies toward a population-specific reference (2021)
  • Author(s): Takayama Jun、Tadaka Shu、Yano Kenji、Katsuoka Fumiki、Gocho Chinatsu、Funayama Takamitsu、Makino Satoshi、Okamura Yasunobu、Kikuchi Atsuo、Sugimoto Sachiyo、Kawashima Junko、Otsuki Akihito、Sakurai-Yageta Mika、Yasuda Jun、Kure Shigeo、Kinoshita Kengo、Yamamoto Masayuki、Tamiya Gen
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 226-226
  • DOI: 10.1038/s41467-020-20146-8
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries (2021)
  • Author(s): Gharahkhani Puya、et al. (Tamiya Gen; 44th in 86 authors)
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 1258-1258
  • DOI: 10.1038/s41467-020-20851-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improved metabolomic data-based prediction of depressive symptoms using nonlinear machine learning with feature selection (2020)
  • Author(s): Takahashi, Y., Ueki, M., Yamada, M. et al.
  • Journal Title: Translational Psychiatry Volume: 10 Issue: 1 Pages: 157-157
  • DOI: 10.1038/s41398-020-0831-9
  • Peer Reviewed / Open Access
• [Journal Article] Artificial intelligence powered statistical genetics in biobanks (2020)
  • Author(s): Narita Akira、Ueki Masao、Tamiya Gen
  • Journal Title: Journal of Human Genetics Volume: 66 Issue: 1 Pages: 61-65
  • DOI: 10.1038/s10038-020-0822-y
  • Peer Reviewed
• [Journal Article] Clustering by phenotype and genome-wide association study in autism (2020)
  • Author(s): Narita Akira, Nagai Masato, Mizuno Satoshi, Ogishima Soichi et al.
  • Journal Title: Translational Psychiatry Volume: 10 Issue: 1 Pages: 290-290
  • DOI: 10.1038/s41398-020-00951-x
  • Peer Reviewed / Open Access
• [Journal Article] Machine learning for effectively avoiding overfitting is a crucial strategy for the genetic prediction of polygenic psychiatric phenotypes (2020)
  • Author(s): Takahashi, Y., Ueki, M., Tamiya, G. et al.
  • Journal Title: Translational Psychiatry Volume: 10 Issue: 1 Pages: 294-294
  • DOI: 10.1038/s41398-020-00957-5
  • Peer Reviewed / Open Access
• [Journal Article] Machine learning to reveal hidden risk combinations for the trajectory of posttraumatic stress disorder symptoms (2020)
  • Author(s): Takahashi Yuta、Yoshizoe Kazuki、Ueki Masao、Tamiya Gen、Zhiqian Yu、Utsumi Yusuke、Sakuma Atsushi、Tsuda Koji、Hozawa Atsushi、Tsuji Ichiro、Tomita Hiroaki
  • Journal Title: Scientific Reports Volume: 10 Issue: 1
  • DOI: 10.1038/s41598-020-78966-z
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide association study identifies new loci for albuminuria in the Japanese population (2020)
  • Author(s): Hiroshi Okuda, Koji Okamoto, Michiaki Abe, Kota Ishizawa, Satoshi Makino, Osamu Tanabe, Junichi Sugawara, Atsushi Hozawa, Kozo Tanno, Makoto Sasaki, Gen Tamiya, Masayuki Yamamoto, Sadayoshi Ito, Tadashi Ishii
  • Journal Title: Clinical and Experimental Nephrology Volume: 印刷中 Issue: 8 Pages: 1-9
  • DOI: 10.1007/s10157-020-01884-x
  • Peer Reviewed / Open Access
• [Journal Article] Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective. (2020)
  • Author(s): Kuriyama S, Metoki H, Kikuya M, Obara T, Ishikuro M, Yamanaka C, Nagai M, Matsubara H, Kobayashi T, 57名略, Yamamoto M.
  • Journal Title: Int J Epidemiol. Volume: 49(1) Issue: 1 Pages: 18-19
  • DOI: 10.1093/ije/dyz169
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of Integrated Biobank for Precision Medicine and Personalized Healthcare: The Tohoku Medical Megabank Project (2019)
  • Author(s): Nobuo Fuse, Mika Sakurai-Yageta, Fumiki Katsuoka, Inaho Danjoh, Ritsuko Shimizu, Gen Tamiya, Fuji Nagami, Hiroshi Kawame, Shinichi Higuchi, Kengo Kinoshita, Shigeo Kure, Masayuki Yamamoto
  • Journal Title: JMA Journal Volume: 2 Issue: 2 Pages: 113-122
  • DOI: 10.31662/jmaj.2019-0014
  • NAID: 130007713815
  • ISSN: 2433-328X, 2433-3298
  • Year and Date: 2019-09-04
  • Peer Reviewed / Open Access
• [Journal Article] Automated acquisition of explainable knowledge from unannotated histopathology images (2019)
  • Author(s): Yamamoto Yoichiro、Tsuzuki Toyonori、Akatsuka Jun、Ueki Masao、Morikawa Hiromu、Numata Yasushi、Takahara Taishi、Tsuyuki Takuji、Tsutsumi Kotaro、Nakazawa Ryuto、Shimizu Akira、Maeda Ichiro、Tsuchiya Shinichi、Kanno Hiroyuki、Kondo Yukihiro、Fukumoto Manabu、Tamiya Gen、Ueda Naonori、Kimura Go
  • Journal Title: Nature Communications Volume: 10 Issue: 1 Pages: 5642-5642
  • DOI: 10.1038/s41467-019-13647-8
  • Peer Reviewed / Open Access
• [Journal Article] Illuminating Clues of Cancer Buried in Prostate MR Image: Deep Learning and Expert Approaches (2019)
  • Author(s): Akatsuka Jun、Yamamoto Yoichiro、Sekine Tetsuro、Numata Yasushi、Morikawa Hiromu、Tsutsumi Kotaro、Yanagi Masato、Endo Yuki、Takeda Hayato、Hayashi Tatsuro、Ueki Masao、Tamiya Gen、Maeda Ichiro、Fukumoto Manabu、Shimizu Akira、Tsuzuki Toyonori、Kimura Go、Kondo Yukihiro
  • Journal Title: Biomolecules Volume: 9 Issue: 11 Pages: 673-673
  • DOI: 10.3390/biom9110673
  • Peer Reviewed / Open Access
• [Journal Article] GWAS with principal component analysis identifies a gene comprehensively controlling rice architecture (2019)
  • Author(s): Yano Kenji、Morinaka Yoichi、Wang Fanmiao、Huang Peng、Takehara Sayaka、Hirai Takaaki、Ito Aya、Koketsu Eriko、Kawamura Mayuko、Kotake Kunihiko、Yoshida Shinya、Endo Masaki、Tamiya Gen、Kitano Hidemi、Ueguchi-Tanaka Miyako、Hirano Ko、Matsuoka Makoto
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 116 Issue: 42 Pages: 21262-21267
  • DOI: 10.1073/pnas.1904964116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In Vivo Expression of NUP93 and Its Alteration by NUP93 Mutations Causing Focal Segmental Glomerulosclerosis. (2019)
  • Author(s): Hashimoto T, Harita Y, Takizawa K, Urae S, Ishizuka K, Miura K, Horita S, Ogino D, Tamiya G, Ishida H, Mitsui T, Hayasaka K, Hattori M.
  • Journal Title: Kidney Int Rep Volume: 4(9) Issue: 9 Pages: 1312-1322
  • DOI: 10.1016/j.ekir.2019.05.1157
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quick assessment for systematic test statistic inflation/deflation due to null model misspecifications in genome-wide environment interaction studies (2019)
  • Author(s): Ueki Masao、Fujii Masahiro、Tamiya Gen、for Alzheimer’s Disease Neuroimaging Initiative and the Alzheimer’s Disease Metabolomics Consortium
  • Journal Title: PLOS ONE Volume: 14 Issue: 7 Pages: e0219825-e0219825
  • DOI: 10.1371/journal.pone.0219825
  • Peer Reviewed / Open Access
• [Journal Article] 3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome (2019)
  • Author(s): Tadaka S. et al. Koshiba S. et al. Kinoshita K.（合計２５名、本研究者は１４番目）
  • Journal Title: Hum Genome Var Volume: 6 Issue: 1 Pages: 28-28
  • DOI: 10.1038/s41439-019-0059-5
  • Peer Reviewed / Open Access
• [Journal Article] The prevalence of GALM mutations that cause galactosemia: A database of functionally evaluated variants (2019)
  • Author(s): Iwasawa Shinya、Kikuchi Atsuo、Wada Yoichi、Arai-Ichinoi Natsuko、Sakamoto Osamu、Tamiya Gen、Kure Shigeo
  • Journal Title: Molecular Genetics and Metabolism Volume: 印刷中 Issue: 4 Pages: 362-367
  • DOI: 10.1016/j.ymgme.2019.01.018
  • Peer Reviewed
• [Journal Article] Estimating carrier frequencies of newborn screening disorders using a whole-genome reference panel of 3552 Japanese individuals (2019)
  • Author(s): Yamaguchi-Kabata, Y.,（途中略）,Koshiba, S., （途中略）, Tohoku Medical Megabank Project Study Group.（合計１9名、本研究者は５番目）
  • Journal Title: Hum. Genet. Volume: 印刷中 Issue: 4 Pages: 389-409
  • DOI: 10.1007/s00439-019-01998-7
  • Peer Reviewed / Open Access
• [Journal Article] Outlier detection for questionnaire data in biobanks (2019)
  • Author(s): Sakurai Rieko、Ueki Masao、Makino Satoshi、Hozawa Atsushi、Kuriyama Shinichi、Takai-Igarashi Takako、Kinoshita Kengo、Yamamoto Masayuki、Tamiya Gen
  • Journal Title: International Journal of Epidemiology Volume: 印刷中 Issue: 4 Pages: 1305-1315
  • DOI: 10.1093/ije/dyz012
  • Peer Reviewed
• [Journal Article] Respiratory resistance among adults in a population-based cohort study in Northern Japan. (2019)
  • Author(s): Miura E, Tsuchiya N, Igarashi Y, Arakawa R, Nikkuni E, Tamai T, Tabata M, Ohkouchi S, Irokawa T, Ogawa H, Takai-Igarashi T, Suzuki Y, Kuriyama S, Tamiya G, Hozawa A, Yamamoto M, Kurosawa H.
  • Journal Title: Respiratory Investigation Volume: 印刷中 Issue: 3 Pages: 30226-0
  • DOI: 10.1016/j.resinv.2018.12.008
  • Peer Reviewed
• [Journal Article] Growth impairment in individuals with citrin deficiency (2019)
  • Author(s): Numakura Chikahiko、Tamiya Gen、Ueki Masao、Okada Tomoo、Maisawa Shun-ichi、Kojima-Ishii Kanako、Murakami Jun、Horikawa Reiko、Tokuhara Daisuke、Ito Koichi、Adachi Masanori、Abiko Takahiro、Mitsui Tetsuo、Hayasaka Kiyoshi
  • Journal Title: Journal of Inherited Metabolic Disease Volume: 42 Issue: 3 Pages: 501-508
  • DOI: 10.1002/jimd.12051
  • Peer Reviewed
• [Journal Article] Susceptibility Loci for Tanning Ability in the Japanese?Population Identified by a?Genome-Wide?Association Study from the Tohoku Medical Megabank Project Cohort Study (2019)
  • Author(s): Shido Kosuke、Kojima Kaname、Yamasaki Kenshi、Hozawa Atsushi、Tamiya Gen、Ogishima Soichi、Minegishi Naoko、Kawai Yosuke、Tanno Kozo、Suzuki Yoichi、Nagasaki Masao、Aiba Setsuya
  • Journal Title: Journal of Investigative Dermatology Volume: epub Issue: 7 Pages: 1605-1608.e13
  • DOI: 10.1016/j.jid.2019.01.015
  • Peer Reviewed / Open Access
• [Presentation] 日本人基準ゲノムJG1の構築とクリニカルシークエンシングへの応用 (2020)
  • Author(s): 田宮 元
  • Organizer: Scientific Meeting in Osaka
  • Invited
• [Presentation] 機械学習・人工知能技術を用いたゲノムリスク予測 (2020)
  • Author(s): 田宮 元
  • Organizer: 第46回東北眼疾患病態研究会
  • Invited
• [Presentation] 日本人基準ゲノム配列を用いた家族性疾患の遺伝子同定 (2019)
  • Author(s): 田宮 元
  • Organizer: 第25回日本家族性腫瘍学会学術集会
  • Invited
• [Presentation] 人工知能・機械学習手法による大規模ゲノムコホート解析 (2019)
  • Author(s): 田宮 元
  • Organizer: 第71回日本皮膚科学会西部支部学術大会
  • Invited
• [Remarks] 東北大学・東北メディカルメガバンク機構・リスク統計解析室
  • URL: http://www.genetix-h.com/~AMERI/index.html