The "Bermuda triangle" of genetics, environment and autoimmunity is involved in 
the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic 
contribution to the etiology, pathogenesis and outcome of RA are discussed in 
this review. The heritability of RA has been estimated to be about 60 %, while 
the contribution of HLA to heritability has been estimated to be 11-37 %. Apart 
from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other 
HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA 
susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P 
and S3D groups, where primarily S2 and S3P groups have been associated with 
predisposition to seropositive RA. The most relevant non-HLA gene single 
nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, 
CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) 
have identified more than 30 loci involved in RA pathogenesis. HLA and some 
non-HLA genes may differentiate between anti-citrullinated protein antibody 
(ACPA) seropositive and seronegative RA. Genetic susceptibility has also been 
associated with environmental factors, primarily smoking. Some GWAS studies 
carried out in rodent models of arthritis have confirmed the role of human 
genes. For example, in the collagen-induced (CIA) and proteoglycan-induced 
arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, 
corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been 
identified. Finally, pharmacogenomics identified SNPs or multiple genetic 
signatures that may be associated with responses to traditional 
disease-modifying drugs and biologics.