Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease
Abstract Background Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease, often remaining asymptomatic until the thyroid is significantly affected. Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to drive many inflammatory diseases and autoi...
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2025-04-01
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| author | Xue Zhang Yuqing Wang Huiwen Xue Yingsuo Zhao Mingcheng Liu Hui Wei Qianwei Liu |
| author_facet | Xue Zhang Yuqing Wang Huiwen Xue Yingsuo Zhao Mingcheng Liu Hui Wei Qianwei Liu |
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| description | Abstract Background Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease, often remaining asymptomatic until the thyroid is significantly affected. Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to drive many inflammatory diseases and autoimmune diseases. The association between CHIP and AITD is scarcely reported. This study aims to investigate whether CHIP is associated with the risk of AITD. Methods We conducted a prospective community-based cohort study at the UK Biobank. CHIP, defined as the exposure, was identified using whole-exome sequencing (WES) data. AITD was sourced from the inpatient hospitalization register, the death register, and the primary healthcare register. Cox regression models were utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between CHIP and AITD. Next, we conducted a subgroup analysis to investigate the role of specific gene mutations (DNMT3A, TET2, ASXL1, PPM1D, SRSF2, and JAK2) in the investigated association. Finally, we assessed the association across small CHIP clones (variant allele frequency, VAF: 2–10%) and large CHIP clones (VAF ≥ 10%). All models were adjusted for sex, age, ethnicity, education, Townsend deprivation index, body mass index, smoking status, and drinking status. Results A total of 454,618 individuals were included in the final analysis. We identified 14,059 (3.1%) participants with CHIP. Compared with individuals without CHIP, those with CHIP were generally older and more likely to be smokers. Over a median follow-up of 12.7 years (interquartile range, IQR: 11.9–13.5), 21,708 cases with AITD were diagnosed. CHIP was associated with an increased risk of AITD (HR 1.11, 95% CI 1.03–1.19). Specifically, individuals with TET2-mutant CHIP (HR 1.23, 95% CI 1.07–1.41) had an elevated risk of AITD. A large CHIP clone (HR 1.17, 95% CI 1.08–1.27) was associated with an increased risk of AITD. Focusing on large CHIP clone, we also observed an association between TET2-mutant (HR 1.27, 95% CI 1.10–1.47) and ASXL1-mutant (HR 1.33, 95% CI 1.02–1.73) CHIP and risk of AITD. Conclusions Individuals with CHIP were associated with a modestly increased risk of AITD, especially TET2-mutant CHIP. Future studies are needed to verify current findings and elaborate potential mechanisms. |
| format | Article |
| id | doaj-art-644162933737434390ceff69ca1a25cd |
| institution | OA Journals |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-644162933737434390ceff69ca1a25cd2025-08-20T02:20:05ZengBMCBMC Medicine1741-70152025-04-012311910.1186/s12916-025-04077-zClonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid diseaseXue Zhang0Yuqing Wang1Huiwen Xue2Yingsuo Zhao3Mingcheng Liu4Hui Wei5Qianwei Liu6State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Hematology, Nanfang Hospital, Southern Medical UniversityDepartment of Hematology, Nanfang Hospital, Southern Medical UniversityDepartment of Hematology, Nanfang Hospital, Southern Medical UniversityState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical CollegeDepartment of Hematology, Nanfang Hospital, Southern Medical UniversityAbstract Background Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease, often remaining asymptomatic until the thyroid is significantly affected. Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to drive many inflammatory diseases and autoimmune diseases. The association between CHIP and AITD is scarcely reported. This study aims to investigate whether CHIP is associated with the risk of AITD. Methods We conducted a prospective community-based cohort study at the UK Biobank. CHIP, defined as the exposure, was identified using whole-exome sequencing (WES) data. AITD was sourced from the inpatient hospitalization register, the death register, and the primary healthcare register. Cox regression models were utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between CHIP and AITD. Next, we conducted a subgroup analysis to investigate the role of specific gene mutations (DNMT3A, TET2, ASXL1, PPM1D, SRSF2, and JAK2) in the investigated association. Finally, we assessed the association across small CHIP clones (variant allele frequency, VAF: 2–10%) and large CHIP clones (VAF ≥ 10%). All models were adjusted for sex, age, ethnicity, education, Townsend deprivation index, body mass index, smoking status, and drinking status. Results A total of 454,618 individuals were included in the final analysis. We identified 14,059 (3.1%) participants with CHIP. Compared with individuals without CHIP, those with CHIP were generally older and more likely to be smokers. Over a median follow-up of 12.7 years (interquartile range, IQR: 11.9–13.5), 21,708 cases with AITD were diagnosed. CHIP was associated with an increased risk of AITD (HR 1.11, 95% CI 1.03–1.19). Specifically, individuals with TET2-mutant CHIP (HR 1.23, 95% CI 1.07–1.41) had an elevated risk of AITD. A large CHIP clone (HR 1.17, 95% CI 1.08–1.27) was associated with an increased risk of AITD. Focusing on large CHIP clone, we also observed an association between TET2-mutant (HR 1.27, 95% CI 1.10–1.47) and ASXL1-mutant (HR 1.33, 95% CI 1.02–1.73) CHIP and risk of AITD. Conclusions Individuals with CHIP were associated with a modestly increased risk of AITD, especially TET2-mutant CHIP. Future studies are needed to verify current findings and elaborate potential mechanisms.https://doi.org/10.1186/s12916-025-04077-zAutoimmune thyroid diseaseClonal hematopoiesis of indeterminate potentialRisk factor |
| spellingShingle | Xue Zhang Yuqing Wang Huiwen Xue Yingsuo Zhao Mingcheng Liu Hui Wei Qianwei Liu Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease BMC Medicine Autoimmune thyroid disease Clonal hematopoiesis of indeterminate potential Risk factor |
| title | Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease |
| title_full | Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease |
| title_fullStr | Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease |
| title_full_unstemmed | Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease |
| title_short | Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease |
| title_sort | clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease |
| topic | Autoimmune thyroid disease Clonal hematopoiesis of indeterminate potential Risk factor |
| url | https://doi.org/10.1186/s12916-025-04077-z |
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