Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases

作者全名：Wen, Jie; Zhang, Jingwei; Zhang, Hao; Zhang, Nan; Lei, Ruoyan; Deng, Yujia; Cheng, Quan; Li, He; Luo, Peng

作者地址：[Wen, Jie; Li, He] Cent South Univ, Hunan Canc Hosp, Anim Lab Ctr, Changsha, Hunan, Peoples R China; [Wen, Jie] Cent South Univ, Affiliated Canc Hosp, Xiangya Sch Med, Changsha, Peoples R China; [Wen, Jie; Zhang, Jingwei; Deng, Yujia; Cheng, Quan] Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China; [Wen, Jie; Zhang, Jingwei; Cheng, Quan] Cent South Univ, Xiangya Hosp, Hypothalam Pituitary Res Ctr, Changsha, Peoples R China; [Wen, Jie; Zhang, Jingwei; Cheng, Quan] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China; [Zhang, Hao] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurosurg, Chongqing, Peoples R China; [Zhang, Nan] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan, Peoples R China; [Lei, Ruoyan] Cent South Univ, Xiangya Sch Med, Changsha, Peoples R China; [Deng, Yujia] Changsha Med Univ, Clin Dept 1, Changsha, Peoples R China; [Luo, Peng] Southern Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou, Peoples R China

通信作者：Li, H (通讯作者)，Cent South Univ, Hunan Canc Hosp, Anim Lab Ctr, Changsha, Hunan, Peoples R China.; Cheng, Q (通讯作者)，Cent South Univ, Xiangya Hosp, Dept Neurosurg, Changsha, Peoples R China.; Cheng, Q (通讯作者)，Cent South Univ, Xiangya Hosp, Hypothalam Pituitary Res Ctr, Changsha, Peoples R China.; Cheng, Q (通讯作者)，Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha, Peoples R China.; Luo, P (通讯作者)，Southern Med Univ, Zhujiang Hosp, Dept Oncol, Guangzhou, Peoples R China.

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001211028200007

JCR分区：Q1

影响因子：6.1

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Air pollutants; Autoimmune disease; Mendelian randomization; TWAS; Causal relationship

摘要：Background Epidemiological evidence links a close correlation between long-term exposure to air pollutants and autoimmune diseases, while the causality remained unknown.Methods Two-sample Mendelian randomization (TSMR) was used to investigate the role of PM10, PM2.5, NO2, and NOX (N = 423,796-456,380) in 15 autoimmune diseases (N = 14,890-314,995) using data from large European GWASs including UKB, FINNGEN, IMSGC, and IPSCSG. Multivariable Mendelian randomization (MVMR) was conducted to investigate the direct effect of each air pollutant and the mediating role of common factors, including body mass index (BMI), alcohol consumption, smoking status, and household income. Transcriptome-wide association studies (TWAS), two-step MR, and colocalization analyses were performed to explore underlying mechanisms between air pollution and autoimmune diseases.Results In TSMR, after correction of multiple testing, hypothyroidism was causally associated with higher exposure to NO2 [odds ratio (OR): 1.37, p = 9.08 x 10-4] and NOX [OR: 1.34, p = 2.86 x 10-3], ulcerative colitis (UC) was causally associated with higher exposure to NOX [OR: 2.24, p = 1.23 x 10-2] and PM2.5 [OR: 2.60, p = 5.96 x 10-3], rheumatoid arthritis was causally associated with higher exposure to NOX [OR: 1.72, p = 1.50 x 10-2], systemic lupus erythematosus was causally associated with higher exposure to NOX [OR: 4.92, p = 6.89 x 10-3], celiac disease was causally associated with lower exposure to NOX [OR: 0.14, p = 6.74 x 10-4] and PM2.5 [OR: 0.17, p = 3.18 x 10-3]. The risky effects of PM2.5 on UC remained significant in MVMR analyses after adjusting for other air pollutants. MVMR revealed several common mediators between air pollutants and autoimmune diseases. Transcriptional analysis identified specific gene transcripts and pathways interconnecting air pollutants and autoimmune diseases. Two-step MR revealed that POR, HSPA1B, and BRD2 might mediate from air pollutants to autoimmune diseases. POR pQTL (rs59882870, PPH4=1.00) strongly colocalized with autoimmune diseases.Conclusion This research underscores the necessity of rigorous air pollutant surveillance within public health studies to curb the prevalence of autoimmune diseases.

基金机构：High Performance Computing Center of Central South University

基金资助正文：The authors express gratitude to the public databases, websites, and software used in the paper. The authors are grateful to the High Performance Computing Center of Central South University for partial support of this work.