Evaluation of the utility of the exposome-wide risk score for the identification of groups at high risk for human disease

• Project/Area Number: 23K18386
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 58:Society medicine, nursing, and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Tajim Atsushi 金沢大学, 医学系, 教授 (10396864)
• Project Period (FY): 2023-06-30 – 2025-03-31
• Project Status: Completed (Fiscal Year 2024)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2024: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2023: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
• Keywords: エクスポソームワイド・リスクスコア / 生活習慣病 / 発症ハイリスク群

Outline of Research at the Start

生涯にわたり曝露される生活・環境因子の総体であるエクスポソームの観点から、エクスポソームワイド・リスクスコア（exposome-wide risk score: ERS）により疾患発症の非遺伝的リスクを集約スコア化する手法を開発し、地域住民コホートを対象として、その有用性を評価する。加えて、特定の生活習慣病に対するERSに基づく発症ハイリスク群に焦点を当て、ハイリスク群に属するにもかかわらず発病しない人たちには、発症の抑制や発症率の低減に関わる共通因子（遺伝、環境、およびそれらの相互作用）が存在するという仮説を設定し、この仮説を立証することを目的とする研究を提案する。

Outline of Final Research Achievements

We estimated the non-genetic risk of developing hypertension and type 2 diabetes for each participant in a population-based cohort, expressing this risk as an exposome-wide risk score (ERS). Using these scores, we identified high-risk groups for each disease. Within these groups, we conducted comparative analyses between individuals who developed the disease and those who did not. We identified statistically significant factors associated with each disease. We performed similar analyses on the remaining 90% of the cohort (i.e., the non-high-risk group) to evaluate the potential of these factors to protect against disease. As a result, we identified candidate protective factors (genetic and environmental) that were commonly observed among participants who did not develop the disease.

Academic Significance and Societal Importance of the Research Achievements

研究開始当初、疫学分野におけるエクスポソームワイド・リスクスコア（ERS）の利活用は、世界的にも端緒についたばかりであった。くわえて、ERSに基づく疾患のハイリスク群に着目し、生活習慣病の発症抑制に関連する遺伝・環境要因を網羅的に探索するという研究課題は、きわめて探索的かつ萌芽的な試みであった。本研究により同定された発症抑制候補因子は、個別化予防や精密医療といった次世代の医療実現に向けた科学的基盤を提供するとともに、生活習慣病の病態理解の深化にも資することが期待される。

Research Products

• [Journal Article] Sex-specific associations between air pollutants and asthma prevalence in Japanese adults: a population-based study (2025)
  • Author(s): Akinori Hara, Takehiro Sato, Sara Kress, Keita Suzuki, Kim-Oanh Pham, Atsushi Tajima, Tamara Schikowski, Hiroyuki Nakamura
  • Journal Title: International journal of environmental health research in press Volume: 35(2) Issue: 2 Pages: 310-318
  • DOI: 10.1080/09603123.2024.2352597
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hepatokine leukocyte cell-derived chemotaxin 2 as a biomarker of insulin resistance, liver enzymes, and metabolic dysfunction-associated steatotic liver disease in the general population (2025)
  • Author(s): Suzuki K, Tsujiguchi H, Hara A, Takeshita Y, Goto H, Nakano Y, Yamamoto R, Takayama H, Tajima A, Yamashita T, Honda M, Nakamura H, Takamura T
  • Journal Title: J Diabetes Investig Volume: 16 Issue: 2 Pages: 298-298
  • DOI: 10.1111/jdi.14351
  • Peer Reviewed / Open Access
• [Journal Article] Sex Differences in the Relationship Between Nutrient Intake and Mortality Results of the Shika Cohort Study (2025)
  • Author(s): Hayashi K, Nakamura M, Tsujiguchi H, Hara A, Suzuki K, Miyagi S, Takazawa C, Zhao J, Camara J, Marama T, Asai A, Katano K, Kasahara T, Sato K, Ogawa A, Fukushima S, Shibata A, Suzuki F, Shimizu Y, Kambayashi Y, Kannon T, Takeshita Y, Tsuboi H, Tajima A, Konoshita T, Takamura T, Nakamura H
  • Journal Title: Nutrients Volume: 17 Issue: 5 Pages: 755-755
  • DOI: 10.3390/nu17050755
  • Peer Reviewed / Open Access
• [Journal Article] Long-term exposure to diesel exhaust particles induces concordant changes in DNA methylation and transcriptome in human adenocarcinoma alveolar basal epithelial cells (2024)
  • Author(s): Lukyanchuk Alexandra、Muraki Naomi、Kawai Tomoko、Sato Takehiro、Hata Kenichiro、Ito Tsuyoshi、Tajima Atsushi
  • Journal Title: Epigenetics & Chromatin Volume: 17 Issue: 1 Pages: 24-24
  • DOI: 10.1186/s13072-024-00549-3
  • Peer Reviewed / Open Access
• [Journal Article] A Supramolecular Biosensor for Rapid and High-Throughput Quantification of a Disease-Associated Niacin Metabolite (2024)
  • Author(s): Ueno Masaya、Sugiyama Hiroki、Kurayoshi Kenta、Kobayashi Masahiko、Tadokoro Yuko、Kasahara Atsuko、Shoulkamy Mahmoud I.、Maeda Katsuhiro、Ogoshi Tomoki、Hirao Atsushi
  • Journal Title: Analytical Chemistry Volume: 96 Issue: 36 Pages: 14499-14507
  • DOI: 10.1021/acs.analchem.4c02653
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between coronary artery disease with dyslipidaemia and trace mineral intake: a cross-sectional analysis of the Shika study (2024)
  • Author(s): Kimura K, Suzuki F, Tsujiguchi H, Hara A, Miyagi S, Kannon T, Suzuki K, Shimizu Y, Nguyen TTT, Katano K, Asai A, Kasahara T, Nakamura M, Takazawa C, Hayashi K, Hamagishi T, Shibata A, Sato T, Nomura A, Konoshita T, Kambayashi Y, Tsuboi H, Tajima A, Kobayashi T, Nakamura H
  • Journal Title: J Nutr Sci Volume: 13
  • DOI: 10.1017/jns.2024.26
  • Peer Reviewed / Open Access
• [Journal Article] Serum TNFα and IL-17A levels may predict increased depressive symptoms: findings from the Shika Study cohort project in Japan (2024)
  • Author(s): Tsuboi Hirohito、Sakakibara Hiroyuki、Minamida-Urata Yuuki、Tsujiguchi Hiromasa、Hara Akinori、Suzuki Keita、Miyagi Sakae、Nakamura Masaharu、Takazawa Chie、Kannon Takayuki、Zhao Jiaye、Shimizu Yukari、Shibata Aki、Ogawa Aya、Suzuki Fumihiko、Kambayashi Yasuhiro、Konoshita Tadashi、Tajima Atsushi、Nakamura Hiroyuki
  • Journal Title: BioPsychoSocial Medicine Volume: 18 Issue: 1 Pages: 20-20
  • DOI: 10.1186/s13030-024-00317-5
  • Peer Reviewed / Open Access
• [Journal Article] Oxytocin Receptor Polymorphism Is Associated With Sleep Apnea Symptoms (2024)
  • Author(s): Goto Hisanori、Yamamoto Yasuhiko、Tsujiguchi Hiromasa、Sato Takehiro、Yamamoto Reina、Takeshita Yumie、Nakano Yujiro、Kannon Takayuki、Hosomichi Kazuyoshi、Suzuki Keita、Nakamura Masaharu、Kambayashi Yasuhiro、Karashima Shigehiro
  • Journal Title: Journal of the Endocrine Society Volume: 9 Issue: 1 Pages: 198-198
  • DOI: 10.1210/jendso/bvae198
  • Peer Reviewed / Open Access
• [Journal Article] Association between animal protein intake, oral frailty and calf circumference in middle-aged and older adults: a cross-sectional analysis from the Shika study (2024)
  • Author(s): Fumihiko Suzuki, Hiroyuki Nakamura（23人中23番目）
  • Journal Title: BMJ Open Volume: 14 Issue: 2 Pages: e078129-e078129
  • DOI: 10.1136/bmjopen-2023-078129
  • Peer Reviewed / Open Access
• [Journal Article] Nutrigenetic Interaction Between Apolipoprotein C3 Polymorphism and Fat Intake in People with Nonalcoholic Fatty Liver Disease (2023)
  • Author(s): Yamamoto Reina、Takeshita Yumie、Tsujiguchi Hiromasa、Kannon Takayuki、Sato Takehiro、Hosomichi Kazuyoshi、Suzuki Keita、Kita Yuki、Tanaka Takeo、Goto Hisanori、Nakano Yujiro、Yamashita Tatsuya、Kaneko Shuichi、Tajima Atsushi、Nakamura Hiroyuki、Takamura Toshinari
  • Journal Title: Current Developments in Nutrition Volume: 7 Issue: 4 Pages: 100051-100051
  • DOI: 10.1016/j.cdnut.2023.100051
  • Peer Reviewed / Open Access
• [Journal Article] Genetic factors associated with serum amylase in a Japanese population: combined analysis of copy-number and single-nucleotide variants (2023)
  • Author(s): Zannatun Nayema, Takehiro Sato, Takayuki Kannon, Hiromasa Tsujiguchi, Kazuyoshi Hosomichi, Hiroyuki Nakamura, Atsushi Tajima
  • Journal Title: Journal of Human Genetics Volume: 68 Issue: 5 Pages: 313-319
  • DOI: 10.1038/s10038-022-01111-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A comprehensive risk factor analysis using association rules in people with diabetic kidney disease (2023)
  • Author(s): Toyama Tadashi、Shimizu Miho、Yamaguchi Taihei、Kurita Hidekazu、Morita Tetsurou、Oshima Megumi、Kitajima Shinji、Hara Akinori、Sakai Norihiko、Hashiba Atsushi、Takayama Takuzo、Tajima Atsushi、Furuichi Kengo、Wada Takashi、Iwata Yasunori
  • Journal Title: Scientific Reports Volume: 13 Issue: 1 Pages: 11690-11690
  • DOI: 10.1038/s41598-023-38811-5
  • Peer Reviewed / Open Access
• [Journal Article] Distinct associations between dietary omega-3 and omega-6 fatty acids intake with chronic kidney disease in adults with and without diabetes: A cross-sectional study (2023)
  • Author(s): Hara Akinori、Tsujiguchi Hiromasa、Suzuki Keita、Nakamura Masaharu、Okada Masaru、Zhao Jiaye、Takazawa Chie、Suzuki Fumihiko、Kasahara Tomoko、Shimizu Yukari、Tsuboi Hirohito、Kannon Takayuki、Tajima Atsushi、Takamura Toshinari、Nakamura Hiroyuki
  • Journal Title: Nutrition Volume: 115 Pages: 112156-112156
  • DOI: 10.1016/j.nut.2023.112156
  • Peer Reviewed / Open Access
• [Journal Article] Genetic Characteristics Contributing to Lipoprotein(a) Levels in the Japanese Population (2023)
  • Author(s): Yamagami Kan、Tada Hayato、Sato Takehiro、Nomura Akihiro、Sakata Kenji、Usui Soichiro、Kawashiri Masa-aki、Tajima Atsushi、Takamura Masayuki
  • Journal Title: Journal of Coronary Artery Disease Volume: 29 Issue: 4 Pages: 104-108
  • DOI: 10.7793/jcad.29.23-00015
  • ISSN: 2434-2173
  • Peer Reviewed / Open Access
• [Presentation] 経験がもたらすラット海馬左右CA1領域における遺伝子発現変化の解析 (2024)
  • Author(s): 久保田梓、纐纈真之介、篠原良章、田嶋敦
  • Organizer: NEURO2024
• [Presentation] Relationship between social capital and objective sleep index: Results of the Shika study (2024)
  • Author(s): Ishizaki M、Miyagi S、Morita E、Hori D、Hara A、Tsujiguchi H、Kambayashi Y、Suzuki F、Hayashi K、Konoshita T、Tsuboi H、Tajima A、Takamura T、Ikaga T、Yanagisawa M、Nakamura H
  • Organizer: APHA 2024
  • Int'l Joint Research
• [Presentation] The association of hyperlipidemia and micronutrient intake with depressive symptoms in middle-aged and elderly Japanese (2024)
  • Author(s): Makimura T、Tsujiguchi H、Hara A、Kambayashi Y、Suzuki F、Hayashi K、Takamura T、Konoshita T、Tsuboi H、Tajima A、Nakamura H
  • Organizer: APHA 2024
  • Int'l Joint Research
• [Presentation] 日本人中高年齢者におけるビタミン摂取量とレジリエンスの関連―志賀町研究による性差の検討― (2024)
  • Author(s): 佐藤邦子、鈴木史彦、辻口博聖、原章規、観音隆幸、宮城栄重、鈴木啓太、中村勝治、高澤千絵、林宏一、柴田亜樹、坪井宏仁、清水由加里、Thao Thi Thu Nguyen、此下忠志、小野靖樹、田嶋敦、中村裕之
  • Organizer: 第21回日本予防医学会学術総会
• [Presentation] 非飲酒の男性において植物性たんぱく質の高摂取、動物性脂質の低摂取は糖尿病の発症を抑制する:志賀町における前向き疫学研究 (2023)
  • Author(s): 小川彩、辻口博聖、中村勝治、林宏一、原章規、鈴木啓太、宮城栄重、觀音隆幸、高澤千絵、趙嘉業、岡田俊、神林康弘、清水由加里、柴田亜樹、此下忠志、鈴木史彦、坪井宏仁、田嶋敦、中村裕之
  • Organizer: 第20回日本予防医学会学術総会
• [Presentation] オーラルフレイルでの体重調整下腿周囲長は動物性タンパク質摂取と関連する：志賀町研究から (2023)
  • Author(s): 鈴木史彦、岡本成史、仲井慎吾、宮城栄重、辻口博聖、原章規、Thao Thi Thu Nguyen、清水由加里、林宏一郎、鈴木啓太、笠原友子、中村勝治、高澤千絵、小川彩、岡田俊、柴田亜樹、觀音隆幸、田嶋敦、坪井宏仁、荻野学芳、此下忠志、篁 俊成、池田裕也、中村裕之
  • Organizer: 第20回日本予防医学会学術総会
• [Presentation] 二酸化窒素（NO2）を曝露したヒト気道上皮の長鎖ノンコーディングRNA（lncRNA）の発現解析 (1) NO2曝露により発現変動するlncRNAの探索 (2023)
  • Author(s): 村木直美、伊藤剛、田村久美子、田嶋敦
  • Organizer: 第64回大気環境学会年会
• [Presentation] 二酸化窒素（NO2）を曝露したヒト気道上皮の長鎖ノンコーディングRNA（lncRNA）の発現解析 (1) NO2曝露により発現変動するlncRNAの探索 (2023)
  • Author(s): 伊藤剛、村木直美、田村久美子、田嶋敦
  • Organizer: 第64回大気環境学会年会
• [Presentation] 様々なアレルギー疾患とHLA遺伝型の関連解析 (2023)
  • Author(s): 中村瑠莉、岩内陽子、観音隆幸、細道一善、田嶋敦
  • Organizer: 第31回日本組織適合性学会
• [Presentation] 客観的な睡眠状態と感覚処理感受性との関連 (2023)
  • Author(s): 辻口博聖、宮城栄重、鈴木啓太、原章規、清水由加里、佐藤丈寛、柴田亜樹、神林康弘、鈴木史彦、坪井宏仁、田嶋敦、伊香賀俊治、池田裕也、中村裕之、筑波大学SLEPT研究グループ
  • Organizer: 日本睡眠学会第45回定期学術集会・第30回日本時間生物学会学術大会 合同大会
• [Presentation] In vitro DNA methylome and transcriptome analysis in human alveolar epithelial cells after long-term exposure of diesel exhaust particles (2023)
  • Author(s): Alexandra Lukyanchuk、Naomi Muraki、Tsuyoshi Ito、Tomoko Kawai、Kenichiro Hata、Kazuyoshi Hosomichi、Takayuki Kannon、Takehiro Sato、Atsushi Tajima
  • Organizer: ISEE 2023
  • Int'l Joint Research
• [Presentation] Usefulness of polygenic risk score for intraventricular septal diameter in patients with hypertrophic cardiomyopathy (2023)
  • Author(s): Akihiro Nomura、Takehiro Sato、Masahiro Noguchi、Yasuaki Takeji、Hayato Tada、Kenshi Hayashi、Atsushi Tajima、Masayuki Takamura、Noboru Fujino
  • Organizer: AHA Scientific Sessions 2023
  • Int'l Joint Research
• [Presentation] トランスクリプトームからみたラット海馬CA1野の左右非対称性の解析 (2023)
  • Author(s): 久保田梓、小嶋健太郎、纐纈真之介、篠原良章、田嶋敦
  • Organizer: 第46回日本分子生物学会年会
• [Remarks] 金沢大学医薬保健研究域医学系 革新ゲノム情報学分野
  • URL: https://big.w3.kanazawa-u.ac.jp