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Genome-wide association study of social isolation in 63,497 Japanese individuals from the general population
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  • Published: 17 February 2026

Genome-wide association study of social isolation in 63,497 Japanese individuals from the general population

  • Hisashi Ohseto  ORCID: orcid.org/0000-0001-6716-90951,
  • Kosuke Inoue2,
  • Ippei Takahashi3,
  • Taku Obara3,4,5,
  • Akira Narita3,4,
  • Mami Ishikuro3,4,
  • Masatsugu Orui1,3,4,
  • Keiko Murakami4,6,
  • Aoi Noda3,4,5,
  • Genki Shinoda3,4,
  • Masato Takase3,4,
  • Naoki Nakaya3,4,
  • Mana Kogure3,4,
  • Rieko Hatanaka3,4,
  • Kumi Nakaya3,4,
  • Ippei Chiba3,4,
  • Sayuri Tokioka3,4,
  • Yuka Kotozaki  ORCID: orcid.org/0000-0002-4659-12007,8,
  • Atsushi Shimizu8,
  • Kozo Tanno7,8,
  • Atsushi Hozawa3,4,
  • Gen Tamiya3,4,9,
  • Naoki Kondo10 &
  • …
  • Shinichi Kuriyama  ORCID: orcid.org/0000-0002-6445-09111,3,4 

Translational Psychiatry , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Clinical genetics
  • Genomics

Abstract

Social isolation, characterized by a lack of social connections with family, friends, and others, is associated with adverse health outcomes. However, the genetic contribution to the susceptibility to social isolation remains unclear. This study aimed to identify genetic loci associated with social isolation using the Lubben Social Network Scale (LSNS-6) in a Japanese population. The Tohoku Medical Megabank Community-Based Cohort Study was conducted between 2013 and 2016. The participants were genotyped using the Affymetrix Axiom Japonica Array. The LSNS-6 was used to assess familial and friend ties through six questions and social isolation statuses were defined using the total scale, family subscale, and friend subscale. Genome-wide association studies (GWASs) were conducted using a generalized linear mixed model, adjusting for age, sex, 10 genetic principal components and batch effects. In total, 63,497 participants who completed genotyping and the LSNS-6 were included. The mean age was 59.4 ± 11.9 years, and 41,126 (64.8%) were female. Significant genetic loci were identified in GWASs for the total scale (rs10736933 near ACADSB and HMX3) and friend subscale of LSNS-6 (rs1778366 near LINC02315 and LRFN5). This study provides the first genome-wide evidence of social isolation in the Japanese population, suggesting associations with ACADSB, HMX3, LINC02315, and LRFN5. These findings could enable personalized prevention and intervention for social isolation and related psychiatric disorders.

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Data availability

Individual data are available upon request after the approval of the Ethical Committee and the Materials and Information Distribution Review Committee of Tohoku Medical Megabank Organization.

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Acknowledgements

The authors would like to thank all the participants who consented to participate in this study and all the staff at the Tohoku Medical Megabank Organization, Tohoku University, Iwate Tohoku Medical Megabank Organization, and Iwate Medical University. A full list of the members of the Tohoku Medical Megabank Organization is available at https://www.megabank.tohoku.ac.jp/english/a250901/. We used the artificial intelligence tool GPT-4 language model, version 4.0, developed by OpenAI, to assist in the initial drafting and editing of this manuscript. It provided suggestions for sentence structure and grammatical corrections. However, all intellectual contributions and final edits were made by the authors.

Funding

This work was supported by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) KAKENHI [grant numbers 19H03894 and 22H03346] and the Japan Agency for Medical Research and Development (AMED) [grant numbers JP21tm0124005 and JP21tm0424601].

Author information

Authors and Affiliations

  1. International Research Institute of Disaster Science, Tohoku University, Sendai, Japan

    Hisashi Ohseto, Masatsugu Orui & Shinichi Kuriyama

  2. Department of Health Promotion and Behavioral Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Kosuke Inoue

  3. Graduate School of Medicine, Tohoku University, Sendai, Japan

    Ippei Takahashi, Taku Obara, Akira Narita, Mami Ishikuro, Masatsugu Orui, Aoi Noda, Genki Shinoda, Masato Takase, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Atsushi Hozawa, Gen Tamiya & Shinichi Kuriyama

  4. Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan

    Taku Obara, Akira Narita, Mami Ishikuro, Masatsugu Orui, Keiko Murakami, Aoi Noda, Genki Shinoda, Masato Takase, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Atsushi Hozawa, Gen Tamiya & Shinichi Kuriyama

  5. Tohoku University Hospital, Tohoku University, Sendai, Japan

    Taku Obara & Aoi Noda

  6. Department of Health and Social Behavior, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Keiko Murakami

  7. Department of Hygiene and Preventive Medicine, Iwate Medical University, Iwate, Japan

    Yuka Kotozaki & Kozo Tanno

  8. Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan

    Yuka Kotozaki, Atsushi Shimizu & Kozo Tanno

  9. RIKEN Center for Advanced Intelligence Project, Tokyo, Japan

    Gen Tamiya

  10. Department of Social Epidemiology, Graduate School of Medicine and School of Public Health, Kyoto University, Kyoto, Japan

    Naoki Kondo

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  1. Hisashi Ohseto
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Contributions

HO, KI, and IT conceptualized and designed the study. HO and IT conducted the statistical analyses and generated the figures. HO drafted the initial version of the manuscript. KI and NK provided conceptual advice on social isolation and contributed to interpretation of the findings. AN (Narita) and GT contributed to the processing, quality control, and interpretation of genomic data. TO, MI, MO, KM, AN (Noda), GS, MT, NN, MK, RH, KN, IC, and ST contributed to data acquisition, cohort management, and data curation within ToMMo. YK, AS, and KT contributed to data acquisition, cohort management, and data curation within IMM. AH and GT provided methodological advice and contributed to interpretation of the findings. SK and NK supervised the study.

Corresponding author

Correspondence to Shinichi Kuriyama.

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KM is an employee of the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other authors have no conflict of interests.

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Individual data are available upon request after the approval of the Ethical Committee and the Materials and Information Distribution Review Committee of Tohoku Medical Megabank Organization.

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Ohseto, H., Inoue, K., Takahashi, I. et al. Genome-wide association study of social isolation in 63,497 Japanese individuals from the general population. Transl Psychiatry (2026). https://doi.org/10.1038/s41398-026-03896-9

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  • Received: 29 September 2024

  • Revised: 21 December 2025

  • Accepted: 01 February 2026

  • Published: 17 February 2026

  • DOI: https://doi.org/10.1038/s41398-026-03896-9

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