Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups.
Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups.
复制标题
系统性红斑狼疮 38 个新位点的鉴定和祖先群体之间的遗传异质性
DOI：
10.1038/s41467-021-21049-y
复制
发表时间：
2021-02-03
影响因子：
16.6
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Wang YF;Zhang Y;Lin Z;Zhang H;Wang TY;Cao Y;Morris DL;Sheng Y;Yin X;Zhong SL;Gu X;Lei Y;He J;Wu Q;Shen JJ;Yang J;Lam TH;Lin JH;Mai ZM;Guo M;Tang Y;Chen Y;Song Q;Ban B;Mok CC;Cui Y;Lu L;Shen N;Sham PC;Lau CS;Smith DK;Vyse TJ;Zhang X;Lau YL;Yang W
系统性红斑狼疮（Systemic lupus erythematosus， SLE）是一种具有高遗传性的世界性自身免疫性疾病，其发病率、严重程度和发病年龄在不同祖先群体中存在差异。以前的基因研究更多地关注欧洲人群，他们似乎受到的影响最小。因此，在祖先群体之间的系统性红斑狼疮的共性、差异和治疗选择背后的遗传变异尚未得到很好的阐明。为了解决这个问题，我们进行了一项全基因组关联研究，将中国人口的样本量增加到现有欧洲研究的水平。鉴定出38个新的slel相关位点和不完全共享的遗传结构。除了人类白细胞抗原（HLA）区域外，9个疾病位点显示出明显的祖先差异，并暗示抗体产生是疾病表现差异的潜在机制。在祖先匹配数据集上进行训练时，多基因风险评分的表现明显更好。这些分析有助于揭示SLE在祖先群体中差异的遗传基础。
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.
登录
查看更多内容
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
4.5
作者：
Cunninghame Graham DS;Morris DL;Bhangale TR;Criswell LA;Syvänen AC;Rönnblom L;Behrens TW;Graham RR;Vyse TJ
通讯作者：
Vyse TJ
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
9.1
作者：
Bousfiha A;Jeddane L;Picard C;Ailal F;Bobby Gaspar H;Al-Herz W;Chatila T;Crow YJ;Cunningham-Rundles C;Etzioni A;Franco JL;Holland SM;Klein C;Morio T;Ochs HD;Oksenhendler E;Puck J;Tang MLK;Tangye SG;Torgerson TR;Casanova JL;Sullivan KE
通讯作者：
Sullivan KE