Identification of the shared genetic architecture underlying seven autoimmune diseases with GWAS summary statistics

Author:

Wang Yuping,Yang Yongli,Jia Xiaocan,Zhao Chenyu,Yang Chaojun,Fan Jingwen,Wang Nana,Shi Xuezhong

Abstract

BackgroundThe common clinical symptoms and immunopathological mechanisms have been observed among multiple autoimmune diseases (ADs), but the shared genetic etiology remains unclear.MethodsGWAS summary statistics of seven ADs were downloaded from Open Targets Genetics and Dryad. Linkage disequilibrium score regression (LDSC) was applied to estimate overall genetic correlations, bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap, and stratified-LDSC partitioned heritability to reveal tissue and cell type specific enrichments. Ultimately, we conducted a novel adaptive association test called MTaSPUsSet for identifying pleiotropic genes.ResultsThe high heritability of seven ADs ranged from 0.1228 to 0.5972, and strong genetic correlations among certain phenotypes varied between 0.185 and 0.721. There was substantial polygenic overlap, with the number of shared SNPs approximately 0.03K to 0.21K. The specificity of SNP heritability was enriched in the immune/hematopoietic related tissue and cells. Furthermore, we identified 32 pleiotropic genes associated with seven ADs, 23 genes were considered as novel genes. These genes were involved in several cell regulation pathways and immunologic signatures.ConclusionWe comprehensively explored the shared genetic architecture across seven ADs. The findings progress the exploration of common molecular mechanisms and biological processes involved, and facilitate understanding of disease etiology.

Funder

National Natural Science Foundation of China

Publisher

Frontiers Media SA

Subject

Immunology,Immunology and Allergy

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