Clonal hematopoiesis of indeterminate potential and risk of autoimmune thyroid disease

作者：Xue Jun Zhang, Yuqing Wang, Huiwen Xue, Yingsuo Zhao, Ming-Cheng Liu, Hui Wei, Qianwei Liu · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-04077-z · 被引用次数：5 · 研究领域：Genetic Associations and Epidemiology、Thyroid Disorders and Treatments、Thyroid Cancer Diagnosis and Treatment

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...