Systematic approach demonstrates enrichment of multiple interactions between non-<i>HLA</i> risk variants and <i>HLA-DRB1</i> risk alleles in rheumatoid arthritis.

ABSTRACT:

Objective

In anti-citrullinated protein antibody positive rheumatoid arthritis (ACPA-positive RA), a particular subset of HLA-DRB1 alleles, called shared epitope (SE) alleles, is a highly influential genetic risk factor. Here, we investigated whether non-HLA single nucleotide polymorphisms (SNP), conferring low disease risk on their own, interact with SE alleles more frequently than expected by chance and if such genetic interactions influence the HLA-DRB1 SE effect concerning risk to ACPA-positive RA.

Methods

We computed the attributable proportion (AP) due to additive interaction at genome-wide level for two independent ACPA-positive RA cohorts: the Swedish epidemiological investigation of rheumatoid arthritis (EIRA) and the North American rheumatoid a

SUBMITTER: Diaz-Gallo LM 

PROVIDER: S-EPMC6161669 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature