Lab Activities

Laboratory for Statistical and Translational Genetics

Research Activities

Chikashi Terao portrait

Team Director

Chikashi Terao

Our overall long-term goal is to realize precision medicine by finding variants, especially population-specific ones, with strong effect sizes. We will accomplish this by integrating germline and somatic information, including gene expression, understanding the basis of complex traits, and constructing accurate evaluation models of the current physiological status of the body and prediction models of diseases and outcomes.

In FY 2025, we contributed to a large-scale international meta-analysis for osteoarthritis. We could increase susceptibility signals from 100 to over 250. Combining the association results with single-cell multi-ome data revealed signal enrichment in embryonic skeletal development pathways. Eight biological processes showed convergent involvement of multiple effector genes, including the circadian clock, glial-cell-related processes and pathways with an established role in osteoarthritis (TGFβ, FGF, WNT, BMP and retinoic acid signaling, and extracellular matrix organization).

We also showed that mosaic chromosomal alteration, cellular expansion with acquired genomic changes, was uniquely associated with a subet of rheumatoid arthritis (RA). Late onset of RA (LORA) has distinct clinical features from young onset RA (YORA). LORA has more male patients, lower heritability, different distribution of synovitis and lower positivity of antibodies. We found that mosaic loss of chromosome Y (mLOY) increased significantly in LORA (odds ratio[OR]=1.43, P = 0.0070), but rather decreased in YORA  (OR=0.66, P = 0.0034). When we analyzed RA as a whole, mLOY did not show significant associations, indicating that we could found the associations by subdividing RA.

observed a negative association between mLOY and YORA. We also found that mLOY with a high cell fraction strengthened the association between PRS and LORA (P = 0.0036). As a conclusion, LORA was characterized by the presence of a high burden of mLOY. The observed interaction between mLOY and PRS in LORA, but not in YORA, supports different gene-environment interactions between the RA subsets.

Mosaic loss of chromosome Y was increased in LORA

Laboratory for Statistical and Translational Genetics figure

Mosaic loss of chromosome Y was increased in LORA

Laboratory for Statistical and Translational Genetics figure

We observed consistent increase of mosaic loss of chromosome Y in LORA and consistent decrease in YORA across data sets.

We observed consistent increase of mosaic loss of chromosome Y in LORA and consistent decrease in YORA across data sets.

Recent Major Publications

  1. Uchiyama S, Ishikawa Y, Ikari K, Honda S, Hikino K, Tanaka E, Kamatani Y, Gono T, Genovese G, Kuwana M, Terao C. Mosaic loss of chromosome Y characterises late-onset rheumatoid arthritis and contrasting associations of polygenic risk score based on age at onset. Ann Rheum Dis 84, 1313–1323 (2025)

  2. Masuo Y, Murakami A, Akamine R, Iri O, Uno S, Murata K, Nishitani K, Ito H, Watanabe R, Fujii T, Iwasaki T, Nakamura S, Kuriyama S, Morita Y, Murakawa Y, Terao C, Okada Y, Hashimoto M, Matsuda S, Ueno H, Yoshitomi H. Stem-like and effector peripheral helper T cells comprise distinct subsets in rheumatoid arthritis. Sci Immunol 10, eadt3955 (2025)

  3. Murakami A, Akamine R, Tanaka S, Murata K, Nishitani K, Ito H, Watanabe R, Fujii T, Iwasaki T, Masuo Y, Iri O, Nakamura S, Kuriyama S, Morita Y, Murakawa Y, Terao C, Okada Y, Hashimoto M, Matsuda S, Ueno H, Yoshitomi H. Human CD4+ T cells regulate peripheral immune responses in rheumatoid arthritis via insulin-like growth factor–like family member 2. Sci Immunol 10, eadr3838 (2025)

  4. Lin Y, Li J, Liu T, Chiou J, Lu H, Ariyoshi K, Uchiyama S, Terao C, Yang J, Chou C, Liang W, Chou I, Lin C, Lin T, Liao C, Huang S, Tsai F. Unraveling the genetic link: causal effects and PRS predictions of adiposity‐related health conditions in East Asian individuals. Obesity 33, 1765–1778 (2025)

  5. Koromina M, Ravi A, Panagiotaropoulou G, Schilder BM, Humphrey J, Braun A, Bigdeli T, Chatzinakos C, Coombes BJ, Kim J, Liu X, Terao C, O’Connell KS, Adams MJ, Adolfsson R, Alda M, Alfredsson L, Andlauer TF, ..., Schall U, Schofield PR, Schulze TG, Scott L, Scott RJ, Serretti A, Smoller JW, Świątkowska B, Soler Artigas M, Stein DJ, Streit F, Toma C, Tooney P, Vawter MP, Vieta E, Vincent JB, Waldman ID, Weickert CS, Weickert T, Witt SH, Hong KS, Ikeda M, Iwata N, Won H, Edenberg HJ, Ripke S, Raj T, Coleman JR, Mullins N. Fine-mapping genomic loci refines bipolar disorder risk genes. Nat Neurosci 28, 1393–1403 (2025)

  6. Wang J, Zheng A, Liu N, Tan Z, Shi Y, Ma T, Luo S, Zhu L, Zhou Z, Yuan F, Li T, Gong Y, Fang J, Liu L, Zhang X, Bae S, Terao C, Chen Z, Li X, Wang G, Qu K, Guo C. Integrative spatial multiomics analysis reveals regulatory mechanisms of VCAM1+ proximal tubule cells in lupus nephritis. Ann Rheum Dis 84, 2021-2033 (2025)

  7. Kosugi S, Terao C. TRsv: simultaneous detection of tandem repeat variations, structural variations, and short indels using long read sequencing data. Genome Biol 26, 246 (2025)

  8. Kobayashi T, Hachiya T, Lu Y, Ikehata Y, China T, Kawano H, Nagata M, Ide H, Isotani S, Nojiri S, Iwami T, Uchiyama S, Okazaki Y, Nakagawa H, Morisaki T, Matsuda K, Kamatani Y, Terao C, Horie S. Local radiotherapy for cancer patients is associated with mosaic loss of chromosome Y, a hallmark of male aging. NPJ Aging 11, 69 (2025)

  9. Hatzikotoulas K, Southam L, Stefansdottir L, Boer CG, McDonald M, Pett JP, Park Y, Tuerlings M, Mulders R, Barysenka A, Arruda AL, Tragante V, Rocco A, Bittner N, Chen S, Horn S, Srinivasasainagendra V, To K, ..., Song Y, Sørensen E, Tamiya G, Tamura Y, Terao C, Thorleifsson G, Troelsen A, Tsezou A, Uchio Y, Uitterlinden AG, Ullum H, Valdes AM, van Heel DA, Walters RG, Weir DR, Wilkinson JM, Winsvold BS, Yamamoto M, Zwart J, Stefansson K, Meulenbelt I, Teichmann SA, van Meurs JB, Styrkarsdottir U, Zeggini E. Translational genomics of osteoarthritis in 1,962,069 individuals. Nature 641, 1217–1224 (2025)

  10. Yoshida N, Stewart DR, Uchimura A, Arita K, Bombard Y, Frone M, Hinoi T, Kamiya K, Katamine S, Kayukawa J, Kodama K, Miller DT, Miura K, Muto K, Nagami F, Nakagawa H, Noda A, Ohishi W, Tanabe O, Terao C, Rajaraman P, Kato K, Biesecker LG. Symposium report—ethical and social considerations regarding return of secondary findings in atomic bomb survivors. Carcinogenesis 46, bgaf059 (2025)

  11. Ortega-Reyes D, Takeuchi T, Ogata Y, Iwami T, Suda W, Kubota T, Kubota N, Kadowaki T, Tomizuka K, Ohno H, Horikoshi M, Terao C. Interplay between host genetics and gut microbiome composition in the Japanese population. Front Microbiomes 4, 1635907 (2025)

  12. Lin Y, Li J, Lai Y, Liu T, Chiou J, Lu H, Ariyoshi K, Terao C, Yang J, Chou C, Liang W, Chou I, Ho C, Lin T, Liao C, Huang S, Tsai F. Blood Pressure Genetics in Han Taiwanese With Cross-Trait Analysis in East Asians: Insights Into Comorbidities, All-Cause Mortality, and Cardiovascular Mortality. Hypertension 82, 2227–2240 (2025)

  13. Koyanagi Y, Murakami Y, Kominami T, Fukushima M, Goto K, Yokota S, Mizobuchi K, Mawatari G, Torii K, Inoue Y, Ota J, Okuda D, Fujiwara K, Yamaga H, Hisai T, Endo M, Iijima H, Kaida T, Miyata K, Nakazaki S, Hayashi T, Hirami Y, Akiyama M, Terao C, Momozawa Y, Sonoda K, Nishiguchi KM, Ikeda Y. Clinical characteristics of EYS-associated retinal dystrophy in 291 Japanese patients. NPJ Genom Med 11, 3 (2025)

  14. Hikino K, Ozaki K, Liu X, Ishikawa Y, Mushiroda T, Terao C. Unraveling time-dependent genetic components underlying alcohol response. Neuropsychopharmacology 50, 1665-1673 (2025)

  15. Hikino K, Fukunaga K, Liu X, Terao C, Mushiroda T. Analysis of factors influencing the relationship between voriconazole plasma concentrations and adverse effects in a paediatric population. Br J Clin Pharmacol 91, 2020-2027 (2025)

ALL