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


