Development of powerful genome-wide gene-gene and gene-environment interaction analysis

• Project/Area Number: 25870074
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Statistical science; Human genetics
• Research Institution: Kurume University (2015); Tohoku University (2013-2014)
• Principal Investigator: Ueki Masao 久留米大学, バイオ統計センター, 准教授 (10515860)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 遺伝的相互作用解析 / ゲノムワイド関連解析 / 高次元回帰モデル / ゲノムワイド遺伝子×遺伝子相互作用

Outline of Final Research Achievements

World-wide genome-wide association studies (GWASs) using single nucleotide polymorphisms (SNPs) have revealed that SNPs explain small portion of variability of human phenotypes, so-called the missing heritability problem. Current standard method which tests each SNP one at a time may miss contributions by gene-gene or gene-environment interactions. However, statistical methods for those hypotheses are still underdeveloped. In this project, a new statistical testing method is developed. It allows to vary the degrees of freedom for test statistics according to the observed cell frequencies. Simulation studies confirmed that a practically adequate statistical power is achieved.
In addition, for genetic prediction problem, new sparse modeling method, smooth-threshold multivariate genetic prediction (STMGP), is developed. It is very rapid even in application to large-scale data such as whole-genome sequencing data, and is shown to have higher prediction accuracy.

Research Products

• [Journal Article] Smooth-threshold multivariate genetic prediction with unbiased model selection (2016)
  • Author(s): Ueki M, Tamiya G
  • Journal Title: Genetic Epidemiology Volume: 40 Issue: 3 Pages: 233-243
  • DOI: 10.1002/gepi.21958
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Immunohistopathological analysis of frizzled-4-positive immature (2015)
  • Author(s): Okamura K, Ohe R, Abe Y, Ueki M, Hozumi Y, Tamiya G, Matsunaga K,
  • Journal Title: Journal of Dermatological Science Volume: 80 Issue: 2 Pages: 156-158
  • DOI: 10.1016/j.jdermsci.2015.07.015
  • Peer Reviewed
• [Journal Article] Sparse predictive modeling for bank telemarketing success using smooth-threshold estimating equations (2015)
  • Author(s): Kawasaki Y, Ueki M
  • Journal Title: Journal of the Japanese Society of Computational Statistics Volume: 28 Pages: 53-66
  • NAID: 130005434011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Positive selection with diversity in oculocutaneous albinisms type 2 gene (OCA2) among Japanese. (2015)
  • Author(s): Shimanuki M, Abe Y, Tamiya G, Ueki M, Hozumi Y, Suzuki T.
  • Journal Title: Pigment Cell Melanoma Res Volume: 28 Issue: 2 Pages: 233-5
  • DOI: 10.1111/pcmr.12337
  • Peer Reviewed
• [Journal Article] On the choice of degrees of freedom for testing gene-gene interactions (2014)
  • Author(s): Ueki, M.
  • Journal Title: Statistics in Medicine Volume: 33 Issue: 28 Pages: 4934-4948
  • DOI: 10.1002/sim.6264
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease. (2014)
  • Author(s): Tamiya G, Makino S, Hayashi M, Abe A, Numakura C, Ueki M, Tanaka A, Ito C, Toshimori K, Ogawa N, Terashima T, Maegawa H, Yanagisawa D, Tooyama I, Tada M, Onodera O, Hayasaka K.
  • Journal Title: Am J Hum Genet. Volume: 95 Issue: 3 Pages: 294-300
  • DOI: 10.1016/j.ajhg.2014.07.013
  • Peer Reviewed / Open Access
• [Journal Article] Pleiotropic effect of common variants at ABO glycosyltranferase locus in 9q32 on plasma levels of pancreatic lipase and angiotensin converting enzyme (2014)
  • Author(s): Yamagata University Genomic Cohort Consortium (YUGCC)
  • Journal Title: PLOS ONE Volume: 9 Issue: 2 Pages: e55903-e55903
  • DOI: 10.1371/journal.pone.0055903
  • Peer Reviewed
• [Journal Article] A pollen coat-inducible autoinhibited Ca^<2+>-ATPase expressed in stigmatic papilla cells is required for compatible pollination in the Brassicaceae (2014)
  • Author(s): Iwano, M., Igarashi, M., Tarutani, Y., Kaothien-Nakayama, P., Nakayama, H., Moriyama, H., Yakabe, R., Entani, T., Shimosato-Asano, H., Ueki, M., Tamiya, G., and Takayama, S
  • Journal Title: Plant Cell Volume: 26 (2) Issue: 2 Pages: 636-649
  • DOI: 10.1105/tpc.113.121350
  • Peer Reviewed
• [Journal Article] Multiple choice from competing regression models under multicollinearity based on standardized update (2013)
  • Author(s): Ueki, M.and Kawasaki, Y.
  • Journal Title: Computational Statistics and Data Analysis Volume: 63 Pages: 31-41
  • DOI: 10.1016/j.csda.2013.01.019
  • Peer Reviewed
• [Journal Article] The confounding effect of cryptic relatedness for environmental risks of systolic blood pressure on cohort studies. (2013)
  • Author(s): Shibata K, Hozawa A, Tamiya G, Ueki M, Nakamura T, et al.
  • Journal Title: Mol Genet Genomic Med Volume: 1 Issue: 1 Pages: 45-53
  • DOI: 10.1002/mgg3.4
  • Peer Reviewed
• [Presentation] 超高次元スパース回帰法によるゲノムデータ解析 (2016)
  • Author(s): 植木優夫, 嶋村海人, 川野秀一, 小西貞則, 田宮元
  • Organizer: 岡山大学IPSR × 九州大学IMI × 理研CSRS シンポジウム 生命データ科学による新たな社会的価値の創造 ～医療、農業、環境分野における役割と作物設計への応用
  • Place of Presentation: 理化学研究所 横浜キャンパス (神奈川)
  • Year and Date: 2016-02-23
  • Invited
• [Presentation] ヒトゲノムデータから見た統計科学 (2016)
  • Author(s): 植木優夫
  • Organizer: 遺伝学と統計学における数理とモデリング
  • Place of Presentation: 政策研究大学院大学 (東京)
  • Year and Date: 2016-01-25
  • Invited
• [Presentation] Multivariate smooth-threshold genetic prediction with unbiased model selection (2015)
  • Author(s): Ueki M, Tamiya G
  • Organizer: East Asia Regional Biometric Conference 2015
  • Place of Presentation: Conference Hall, Kyushu University Station-I for Collaborative Research (福岡)
  • Year and Date: 2015-12-20
  • Int'l Joint Research / Invited
• [Presentation] Smooth-threshold multivariate genetic prediction with unbiased model selection (2015)
  • Author(s): Ueki M, Tamiya G
  • Organizer: 広島統計談話会
  • Place of Presentation: 放射線影響研究所 (広島)
  • Year and Date: 2015-12-04
  • Invited
• [Presentation] 円滑閾値型推定方程式による遺伝的予測 (2015)
  • Author(s): 植木優夫, 田宮元
  • Organizer: 科研費シンポジウム: 生命科学データ解析の方法論と健康科学への応用
  • Place of Presentation: 東京大学 医科学研究所(東京)
  • Year and Date: 2015-10-16
• [Presentation] Bayesian generalized fused lasso modeling via NEG distribution (2015)
  • Author(s): 嶋村海人, 植木優夫, 小西貞則
  • Organizer: 2015年度 統計関連学会連合大会
  • Place of Presentation: 岡山大学 津島キャンパス(岡山)
  • Year and Date: 2015-09-06
• [Presentation] 円滑閾値型推定方程式による遺伝的予測 (2015)
  • Author(s): 植木優夫, 田宮元
  • Organizer: 2015年度 統計関連学会連合大会
  • Place of Presentation: 岡山大学 津島キャンパス(岡山)
  • Year and Date: 2015-09-06
• [Presentation] ゲノムワイドな遺伝子x遺伝子間相互作用の探索 (2015)
  • Author(s): 植木優夫
  • Organizer: 科学研究費・基盤研究(A)「非対称・非線形統計理論と経済・生体科学への応用」 シンポジウム 「バイオ統計学の挑戦と貢献」
  • Place of Presentation: 九州大学医学部百年講堂（福岡県福岡市）
  • Year and Date: 2015-02-02 – 2015-02-04
• [Presentation] Choosing multiple good regression models under multicollinearity (2014)
  • Author(s): Ueki M, Kawasaki Y
  • Organizer: CSA-KSS-JSS joint International Session
  • Place of Presentation: National Chiao Tung University (Taipei, Taiwan)
  • Year and Date: 2014-12-06
  • Invited
• [Presentation] ゲノムワイド疾患関連解析における統計的諸問題 (2014)
  • Author(s): 植木優夫
  • Organizer: 第13回久留米大学バイオ統計学フォーラム
  • Place of Presentation: ＪＲ博多シティ（福岡県福岡市）
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] 遺伝子x遺伝子間相互作用検定の自由度について (2014)
  • Author(s): 植木優夫
  • Organizer: 2014年度統計関連学会連合大会
  • Place of Presentation: 東京大学本郷キャンパス（東京都）
  • Year and Date: 2014-09-13 – 2014-09-16
• [Presentation] Ultrahigh-dimensional variable selection for genome-wide SNP-SNP interaction analysis (2014)
  • Author(s): Ueki M, Tamiya G
  • Organizer: The 3rd Institute of Mathematical Statistics Asia Pacific Rim Meeting
  • Place of Presentation: Howard International House (Taipei, Taiwan)
  • Year and Date: 2014-06-29 – 2014-07-03
  • Invited
• [Presentation] Variable selection method for genome-wide SNP-SNP interaction analysis (2013)
  • Author(s): Ueki M
  • Organizer: 2nd International Symposium on Statistical Genetics (ISSG)
  • Place of Presentation: Korea, Seoul (Seoul National University)
  • Invited
• [Presentation] Variable selection method for whole-genome gene-gene interaction analysis (2013)
  • Author(s): Ueki M, Tamiya G
  • Organizer: Joint Meeting of the IASC Satellite Conference for the 59th ISI WSC and the 8th Conference of the Asian Regional Section(ARS) of the IASC
  • Place of Presentation: Korea, Seoul (Yonsei University)
  • Invited
• [Presentation] ゲノムワイドSNP-SNP相互作用解析 (2013)
  • Author(s): 植木優夫
  • Organizer: 2013年度統計関連学会連合大会
  • Place of Presentation: 豊中市（大阪大学）
  • Invited
• [Book] ゲノム医学のための遺伝統計学 (2015)
  • Author(s): 田宮元、植木優夫、小森理
  • Total Pages: 264
  • Publisher: 共立出版
• [Remarks] 東北大学プレスリリース
  • URL: http://www.tohoku.ac.jp/japanese/2016/04/press20160415-02.html