Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset.

ABSTRACT:

Objectives

To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets.

Methods

We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and ~1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen).

Results

We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. M

SUBMITTER: Saevarsdottir S 

PROVIDER: S-EPMC9279832 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature