American journal of clinical and experimental immunology · 2025
Causal effects and metabolite mediation of immune cells in preterm birth: a Mendelian randomization study.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhou Tong, Zhang Yanqiu, Zhang Sheng, Cao Jun, Feng Bin, Jin Jieyu, Tang Qingqin, Qiu Jun, Qiao Longwei, Liang Yuting
Аннотация
BACKGROUND: Preterm birth poses significant risks to neonatal health. Although immune dysregulation has been implicated in its etiology, the causal roles of specific immune cell phenotypes and the potential mediating effects of metabolites remain unclear. This study applied Mendelian randomization (MR) to investigate causal relationships between immune cell phenotypes and preterm birth, and to assess whether plasma metabolites mediate these associations.
METHODS: Two-sample and mediation MR analyses were performed using genetic variants from genome-wide association studies (GWAS) of immune cells and plasma metabolites. Causal estimates were primarily derived using inverse variance weighting (IVW), with sensitivity analyses conducted via MR-Egger, MR-PRESSO, and leave-one-out validation.
RESULTS: A total of 28 immune cell phenotypes and 47 metabolites were robustly associated with preterm birth (P < 0.05). Reverse MR analysis revealed no evidence of reverse causality for the identified immune phenotypes. Among these, CD28- CD8br AC exhibited the strongest association with increased preterm birth risk. Mediation analysis demonstrated that the effect of CD28- CD8br AC on preterm birth (total effect: 0.148; IVW OR [95% CI]: 1.160 [1.056-1.274], P = 0.002) was partially mediated by isoleucine levels (mediation proportion: 6.79%; P = 0.027) and the acetylcarnitine-to-propionylcarnitine (C2/C3) ratio (mediation proportion: 7.35%; P = 0.029). Sensitivity analyses confirmed the robustness of these findings.
CONCLUSION: This study establishes causal links between immune cell phenotypes, metabolites, and genetic susceptibility to preterm birth. Specifically, CD28- CD8br AC may elevate preterm birth risk through modulation of isoleucine and the C2/C3 ratio, providing novel insights into disease mechanisms and potential therapeutic targets.
METHODS: Two-sample and mediation MR analyses were performed using genetic variants from genome-wide association studies (GWAS) of immune cells and plasma metabolites. Causal estimates were primarily derived using inverse variance weighting (IVW), with sensitivity analyses conducted via MR-Egger, MR-PRESSO, and leave-one-out validation.
RESULTS: A total of 28 immune cell phenotypes and 47 metabolites were robustly associated with preterm birth (P < 0.05). Reverse MR analysis revealed no evidence of reverse causality for the identified immune phenotypes. Among these, CD28- CD8br AC exhibited the strongest association with increased preterm birth risk. Mediation analysis demonstrated that the effect of CD28- CD8br AC on preterm birth (total effect: 0.148; IVW OR [95% CI]: 1.160 [1.056-1.274], P = 0.002) was partially mediated by isoleucine levels (mediation proportion: 6.79%; P = 0.027) and the acetylcarnitine-to-propionylcarnitine (C2/C3) ratio (mediation proportion: 7.35%; P = 0.029). Sensitivity analyses confirmed the robustness of these findings.
CONCLUSION: This study establishes causal links between immune cell phenotypes, metabolites, and genetic susceptibility to preterm birth. Specifically, CD28- CD8br AC may elevate preterm birth risk through modulation of isoleucine and the C2/C3 ratio, providing novel insights into disease mechanisms and potential therapeutic targets.