ARD: biological insights into systemic lupus erythematosus from immune cell-specific transcriptome association studies

OBJECTIVE : Genome-wide association studies (GWAS) have identified more than 100 risk loci for systemic lupus erythematosus (SLE) , but disease genes at most loci remain unclear, hindering translation of these gene discoveri.

The study aimed to prioritize genes for the 110 SLE loci identified in the latest East Asian GWAS meta - analysi.

OBJECTIVE : Genome-wide association studies (GWAS) have identified more than 100 systemic lupus erythematosus (SLE) risk loci, but disease genes at most loci remain unclear, hindering translation of these gene discoveri.

The study aimed to prioritize genes for the 110 SLE loci identified in the latest East Asian GWAS meta - analysi.

Methods : We established gene expression prediction models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells, and peripheral blood cells of 105 Japanes.

Transcriptome-wide association studies (TWAS) were performed using data from a recent genome-wide association meta-analysis of 208,370 East Asians , and candidate genes were searched using TWAS and three data-driven computational approache.

Methods : We established a gene expression prediction model in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanes.

Transcriptome-wide association studies (TWAS) were performed using data from a recent genome-wide association meta-analysis of 208,370 East Asians , and candidate genes were searched using TWAS and three data-driven computational approache.

Results : TWAS identified 171 SLE genes ( p<0 × 10 ^-5 ); 114 (67%) were significant only in a single cell type; 127 (73%) were located in the SLE GWAS locu.

TWAS identified a strong association between CD83 and SLE ( p< ⁷ × 10-8 .

^{A meta -} analysis of genomic associations in existing 208,370 East Asians and an additional 1,498 SLE cases and 3,330 controls found rs72836542 around CD83 ( OR =11 , p=5 × 10-9

) with a new single-gene variant associati.

For the 110 SLE loci , the researchers identified 276 candidate genes, including 104 genes at the recently discovered new SLE loc.

It was demonstrated in vitro that the putative causal variant rs61759532 exhibited allele-specific regulation of ACAP1 and that the presence of the SLE risk allele reduced ACAP1 expressio.

RESULTS : TWAS identified 171 SLE genes ( p <0 × 10 ^{-5 -5} ); 114 (67%) were only significant in a single cell type; 127 (73%) were located in the SLE GWAS locu.

TWAS identified a strong association between CD83 and SLE ( p<7 × 10 ^{-8 -8} .

A meta-analysis of genomic associations in existing 208,370 East Asians and an additional 1,498 SLE cases and 3,330 controls found rs72836542 around CD83 CD83 ( OR =11 ,

There was a new single-gene variant association at p=5 × 10 ^{-9 -9 )}