Department of Dermatology, The First Hospital of China Medical University, National Health Commission Key Laboratory of Immunodermatology, Key Laboratory of Immunodermatology of Ministry of Education, Shenyang, China.
Department of Allergy and Rheumatology, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, China.
J Invest Dermatol. 2023 Jan;143(1):67-77.e15. doi: 10.1016/j.jid.2022.07.012. Epub 2022 Aug 4.
Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseases‒associated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.
虽然慢性自发性荨麻疹（CSU）是一种常见疾病，但针对 CSU 的 GWAS 研究却很少。我们旨在通过对中国汉族成人 CSU 患者进行 GWAS 来鉴定易感性 SNP。发现队列包括 430 例 CSU 病例和 482 例健康对照者。GWAS 结果在 800 例 CSU 病例和 900 例健康对照者中得到验证。对全基因组显著 SNP 进行遗传、功能富集和生物信息学分析，以评估 CSU 与自身免疫或特应性之间的关联。鉴定出 5 个全基因组显著 SNP：rs434124/LILRA3、rs61986182/IGHG1/2、rs73075571/TDGF1、rs9378141/HLA-G 和 rs3789612/PTPN22。前四个 SNP 与自身免疫性疾病相关 SNP 连锁不平衡，并且是免疫细胞中的顺式表达数量性状基因座。这 5 个 SNP 注释基因在免疫过程中显著富集。rs3789612∗T、rs9378141∗C 和 rs73075571∗G 的多基因风险评分和等位基因频率较高与自身免疫性相关的 CSU 表型显著相关，包括抗甲状腺球蛋白 IgG 阳性、抗 FcεRIα IgG 阳性、总 IgE<40IU/ml 和抗甲状腺过氧化物酶 IgG 阳性，但与特应性或过敏致敏 CSU 表型无关。这项 CSU 的 GWAS 确定了五个风险位点，并揭示了 CSU 与自身免疫性疾病存在遗传重叠，并且易患 CSU 的遗传因素主要通过与自身免疫特征的关联来表现。
