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
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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