Identification of 38 Novel Loci for Systemic Lupus Erythematosus and Genetic Heterogeneity Between Ancestral Groups

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Feb 4

PMID 33536424

Citations 107

Authors

Yong-Fei Wang

Yan Zhang

Zhiming Lin

Huoru Zhang

Ting-You Wang

Yujie Cao

David L Morris

Yujun Sheng

Xianyong Yin

Shi-Long Zhong

Xiaoqiong Gu

Yao Lei

Jing He

Qi Wu

Jiangshan Jane Shen

Jing Yang

Tai-Hing Lam

Jia-Huang Lin

Zhi-Ming Mai

Mengbiao Guo

Yuanjia Tang

Yanhui Chen

Qin Song

Bo Ban

Chi Chiu Mok

Yong Cui

Liangjing Lu

Nan Shen

Pak C Sham

Chak Sing Lau

David K Smith

Timothy J Vyse

Xuejun Zhang

Yu Lung Lau

Wanling Yang

Affiliations

Soon will be listed here.

Abstract

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.

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