Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Nat Commun. 2021 Feb 3;12(1):772. doi: 10.1038/s41467-021-21049-y.
Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.
系统性红斑狼疮（SLE）是一种具有高度遗传性的全球性自身免疫性疾病，在不同祖先群体中的患病率、严重程度和发病年龄存在差异。先前的遗传研究主要集中在欧洲人群，而欧洲人群似乎受影响最小。因此，尚未充分阐明 SLE 在不同祖先群体中的共性、差异和治疗选择所涉及的遗传变异。为了解决这一问题，我们进行了全基因组关联研究，将中国人群的样本量增加到与现有欧洲研究相当的水平。确定了 38 个新的与 SLE 相关的基因座，以及不完全共享的遗传结构。除了人类白细胞抗原（HLA）区域外，九个疾病基因座显示出明显的祖先差异，并暗示抗体产生可能是疾病表现差异的潜在机制。基于匹配祖先的数据集进行训练时，多基因风险评分的表现要好得多。这些分析有助于揭示不同祖先群体中 SLE 存在差异的遗传基础。
