Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups
Autor: | Jing Yang, Yao Lei, Timothy J. Vyse, Tai Hing Lam, Pak C. Sham, Liangjing Lu, Yujun Sheng, Chak Sing Lau, Ting-You Wang, Yu-Lung Lau, Shi Long Zhong, Yujie Cao, Huoru Zhang, Mengbiao Guo, Wanling Yang, Bo Ban, Jia Huang Lin, David L. Morris, Yuanjia Tang, David K. Smith, Nan Shen, Qin Song, Yanhui Chen, Yong-Fei Wang, Jing He, Chi Chiu Mok, Zhiming Lin, Qi Wu, Xianyong Yin, Xuejun Zhang, Yong Cui, Yan Zhang, Jiangshan Jane Shen, Zhi Ming Mai, Xiaoqiong Gu |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Linkage disequilibrium Genotype Autoimmune diseases Science General Physics and Astronomy Autoimmunity Human leukocyte antigen Biology Polymorphism Single Nucleotide Genome-wide association studies Linkage Disequilibrium White People Article General Biochemistry Genetics and Molecular Biology Genetic Heterogeneity 03 medical and health sciences Systemic lupus erythematosus 0302 clinical medicine Asian People immune system diseases Genetic variation medicine Humans Lupus Erythematosus Systemic Genetic Predisposition to Disease skin and connective tissue diseases 030203 arthritis & rheumatology Genetics Multidisciplinary Lupus erythematosus Genetic heterogeneity General Chemistry Heritability medicine.disease Genetic architecture 030104 developmental biology Case-Control Studies Age of onset Genome-Wide Association Study |
Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications |
ISSN: | 2041-1723 |
Popis: | 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. The presentation of systemic lupus erythematosus has been known to differ by ancestry, but the underlying genetic factors remain unclear. Here, the authors report ancestry-specific susceptibility loci and better risk prediction when using data from matched ancestral groups. |
Databáze: | OpenAIRE |
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